E.R. Kinkead

Petroleum hydrocarbon toxicity studies

Abstract The suggested hygienic standard of 0.44 mg/liter (90 ppm) is based solely upon animal response to inhalation of “60 Solvent” vapor. Rats were affected at 0.85 mg/liter (170 ppm), but this concentration as well as 1.7 mg/liter (350 ppm) was well tolerated by human volunteers in sensory threshold studies. The LC50 for rats that inhaled the vapor for 4 hr was 24 (22–30) mg/liter or 4900 (4500–6100) ppm. Half this concentration caused loss of coordination, but 3.4 mg/liter (690 ppm) caused no visible response. Similar responses occurred in beagles at 9.5 mg/liter (1900 ppm) and 4.0 mg/liter (820 ppm). Cats died within 4 hr at 20 mg/liter (4100 ppm). The rat Lt50 was 150 min at 38.0 mg/liter (7700 ppm). There were slight increases in liver and kidney weights of beagles on the 5.7- and 2.8-mg/liter levels after 65 exposures (6 hr/day) with no other findings statistically significant. Dilated kidney tubules and pink homogeneous material at the cortico-medullary junction were found in rats that had inhaled 5.7, 2.8, and 1.4 mg/liter (1200, 570, and 290 ppm, respectively), for 13 weeks. In an extension of this study with rats only at 0.85, 0.44, and 0.20 mg/liter (170, 90, and 41 ppm, respectively), there was a statistically significant increased frequency of moderate kidney tubular regeneration and, in our opinion, an unrelated decrease in blood urea nitrogen after 13 weeks of inhalation of 0.85 mg/liter. The odor threshold, as determined by 6 people, was approximately 0.01 mg/liter (2 ppm). Based upon 15-min inhalation periods by humans and the animal findings, the concentration judged acceptable for 8 hr/day, 5 days/week of inhalation was 0.44 mg/liter (90 ppm).

Petroleum hydrocarbon toxicity studies: III. Animal and human response to vapors of Stoddard Solvent

Abstract The suggested hygienic standard for inhalation of Stoddard Solvent for man is 1.2 mg/liter (200 ppm) based upon the results of inhalation studies with rats and dogs and sensory response of human subjects. Inhalation of 8.2 mg/liter (1400 ppm), substantial saturation at 25°C, caused the death of 1 of 15 rats at the termination of 8 hr. Beagle dogs had clonic spasms in 5 hr and cats died between 2.5 and 7.5 hr in roughly equivalent concentrations after signs indicative of central nervous system effect. There were no statistically significant differences between the controls and groups of beagle dogs that inhaled 1.9 mg/liter (330 ppm), 1.1 mg/liter (190 ppm) and 0.48 mg/liter (84 ppm) 6 hr daily, 5 days/wk for 13 wk or 65 exposure days in any of the criteria used for hematology, clinical chemistry, and histopathology. However, rats exposed to 1.9 mg/liter (330 ppm) level for 65 days exhibited slight pathological changes in the kidney, which were related at least in part to the inherent murine nephrosis of the Harlan-Wistar rats employed. The odor threshold as determined in a sniff test by six people is below 0.005 mg/liter (0.9 ppm). In a 15-min inhalation period only slight eye irritation was reported by one of six persons at 0.85 mg/liter (150 ppm). Olfactory fatigue occurred in a short time but 10 min in fresh air restored acuity.

Petroleum hydrocarbon toxicity studies. V. Animal and human response to vapors of mixed xylenes

Abstract The suggested hygienic standard of 0.46 mg/liter (110 ppm) for mixed xylenes is based solely on sensory response of human subjects because of the relatively low toxicity of the vapor. The Lt50 was 92 min for rats that inhaled 46 mg/liter (11,000 ppm) of mixed xylenes, a concentration which approaches air saturated at room temperature. The LC50 for rats in a 4-hr inhalation period was 29 mg/liter (6700 ppm). Cats succumbed within 2 hr at 41 mg/liter (9500 ppm) with signs suggestive of central nervous system effect. No statistically significant differences from control groups, receiving only the uniformly shared dilution air, occurred among groups of beagles and rats that inhaled measured concentrations 6 hr/day, 5 days/wk for 13 wk at levels of 3.5(810), 2.0(460), and 0.77 mg/liter (180 ppm). The odor threshold was determined by a panel of six people to be on the order of 0.0045 mg/liter or 1 ppm. In a 15-min inhalation period, the only common sign of discomfort at 2.0 mg/liter (460 ppm) was eye irritation in four of six subjects. Some transitory olfactory fatigue occurred with recovery in 10 min.

Petroleum hydrocarbon toxicity studies: I. Methodology☆

Abstract The objectives, protocols, and procedures followed in the study of the inhalation toxicity of a series of petroleum hydrocarbons are presented herein. To conserve journal space reference will be made to this report in order to avoid repetition in succeeding reports on selected commercially available petroleum hydrocarbons. The compounds are arranged in a matrix based on boiling range and aromaticity. It is hoped that the information gathered in this series of 12 or more studies will provide a basis for predicting the toxicity of closely related hydrocarbon mixtures that are articles of commerce.

Petroleum hydrocarbon toxicity studies: VI. Animal and human responses to vapors of “60 Solvent”

Abstract The suggested hygienic standard of 0.44 mg/liter (90 ppm) is based solely upon animal response to inhalation of “60 Solvent” vapor. Rats were affected at 0.85 mg/liter (170 ppm), but this concentration as well as 1.7 mg/liter (350 ppm) was well tolerated by human volunteers in sensory threshold studies. The LC50 for rats that inhaled the vapor for 4 hr was 24 (22–30) mg/liter or 4900 (4500–6100) ppm. Half this concentration caused loss of coordination, but 3.4 mg/liter (690 ppm) caused no visible response. Similar responses occurred in beagles at 9.5 mg/liter (1900 ppm) and 4.0 mg/liter (820 ppm). Cats died within 4 hr at 20 mg/liter (4100 ppm). The rat Lt50 was 150 min at 38.0 mg/liter (7700 ppm). There were slight increases in liver and kidney weights of beagles on the 5.7- and 2.8-mg/liter levels after 65 exposures (6 hr/day) with no other findings statistically significant. Dilated kidney tubules and pink homogeneous material at the cortico-medullary junction were found in rats that had inhaled 5.7, 2.8, and 1.4 mg/liter (1200, 570, and 290 ppm, respectively), for 13 weeks. In an extension of this study with rats only at 0.85, 0.44, and 0.20 mg/liter (170, 90, and 41 ppm, respectively), there was a statistically significant increased frequency of moderate kidney tubular regeneration and, in our opinion, an unrelated decrease in blood urea nitrogen after 13 weeks of inhalation of 0.85 mg/liter. The odor threshold, as determined by 6 people, was approximately 0.01 mg/liter (2 ppm). Based upon 15-min inhalation periods by humans and the animal findings, the concentration judged acceptable for 8 hr/day, 5 days/week of inhalation was 0.44 mg/liter (90 ppm).

Petroleum hydrocarbon toxicity studies: VII. Animal and human response to vapors of “70 Solvent”

Abstract The suggested hygienic standard for human inhalation of “70 Solvent”, based upon the results of inhalation studies with rats and dogs and the sensory response of human subjects, is 0.32 mg/liter (59 ppm). Inhalation of 4.4 mg/liter (810 ppm) for 8 hr caused lacrimation, loss of coordination, and fine tremors but no deaths among 10 rats. During the 4-hr inhalation of 5 mg/liter (930 ppm), a beagle had convulsions in 2 hr and died 1.5 hr subsequent to the exposure. Four cats that inhaled 2.0 mg/liter (370 ppm) for 6 hr had signs indicative of central nervous system effect. At a concentration of 2.2 mg/liter (410 ppm) body weights of rats and dogs were slightly depressed only after the 13 th week of inhalation. The adjacent level, 1.1 mg/liter (200 ppm), was considered the no-ill-effect level for both species. The odor threshold, as determined by a sniff test involving six human subjects, is approximately 0.004 mg/liter (0.7 ppm). Only minimal responses were elicited by the six subjects during a 15-min period in 0.32 mg/liter (59 ppm) while, at 0.95 mg/liter (180 ppm), ocular and nasal irritation was reported by five and three subjects, respectively. Therefore, a concentration of 0.32 mg/liter (59 ppm) should be tolerated by most individuals.

Petroleum hydrocarbon toxicity studies: II. Animal and human response to vapors of Varnish Makers' and Painters' Naphtha☆☆☆

Abstract The suggested hygienic standard for inhalation of Varnish Makers and Painters Naphtha (VM&P naphtha) for man is 2.0 mg/liter (430 ppm) based upon inhalation studies with rats and dogs and the sensory response of human subjects. Inhalation of substantially saturated vapor for more than a few minutes constitutes a hazard to life. Rats tolerated saturated vapor at room temperature for 7.5 min but loss of coordination and convulsions occurred in 15 min or more. The single 4-hr inhalation LC50 for rats was 16 mg/liter (3400 ppm), and the highest concentration producing no visible signs of discomfort was 4.4 mg/liter (940 ppm). Rats that survived the 65-day inhalation schedule of 5.8, 2.8, and 1.3 mg/liter (1200, 600, and 280 ppm) were challenged with 27 mg/liter (5800 ppm) for 6 hr. All treated rats were more resistant in terms of mortality than were either their air controls or naive controls of the same age and sex. Only the rats at the 2.8-mg/liter level showed any tendency to prolong the median time to death. Cats responded with signs indicative of severe central nervous system effect when subjected to 19 mg/liter (4100 ppm) for 4 hr. All cats survived the 4-hr exposure, which indicates they are at least as resistant as rats to single 4-hr inhalation. There were no dosage-related statistically significant differences between the controls and the rats and beagles that inhaled 2.8 mg/liter or 1.3 mg/liter for 6 hr daily, 5 days each week for 13 wk. The odor threshold for VM&P naphtha as determined in sniff tests by a panel of six people was found to be on the order of 0.004 mg/liter (0.86 ppm). During a 15-min inhalation period, four of seven subjects had upper respiratory tract irritation and three of seven eye irritation at 4.1 mg/liter (880 ppm). Olfactory fatigue occurred but 10 min in fresh air restored acuity.

Petroleum hydrocarbon toxicity studies: VIII. Animal and human response to vapors of “140° Flash Aliphatic Solvent”☆☆☆

Abstract The suggested hygienic standard for human inhalation of “140° Flash Aliphatic Solvent”, based upon the results of inhalation studies with rats and dogs and upon the sensory response of human subjects is 0.23 mg/liter (37 ppm), the highest vapor level obtained at ambient temperature. Inhalation by rats of concentrations of vaporaerosol in excess of 1.9 mg/liter for 8 hr caused irritation of the extremities and slight loss of coordination but no deaths. During the 8-hr inhalation of essentially saturated vapor (0.21 mg/liter, 33 ppm) at 25°C, one beagle had transitory lacrimation but no other signs of distress. Four cats that inhaled saturated vapor and perhaps some aerosol for 6 hr showed no signs indicative of central nervous system effect. Following inhalation of a concentration of 0.23 mg/liter (37 ppm), 5 days/week, 6 hr/day for 72 and 73 days, respectively, body weights of rats and dogs were not affected nor were there any hematological, biochemical, or histopathological abnormalities discovered. This concentration, which represents air approximately saturated with the vapor at room temperature, was considered the no-ill-effect level for both species. The odor threshold, as determined by a sniff test involving six human subjects, was approximately 0.004 mg/liter (0.6 ppm). During a 15-min period in approximately saturated vapor at room temperature the only evidence of discomfort was mild, nonpersistent irritation in one of six human subjects.

Petroleum hydrocarbon toxicity studies. IV. Animal and human response to vapors of Rubber Solvent

Abstract The suggested hygienic standard for inhalation of Rubber Solvent for man is 1.7 mg/liter (430 ppm) based upon inhalation studies with rats and dogs and the sensory response of human subjects. The LC50 for rats by 4 hr inhalation is 61 mg/liter (15,000 ppm). A concentration of 11 mg/liter (2800 ppm) caused no visible signs of discomfort in rats in 4 hr while for dogs the corresponding concentration was 5.9 mg/liter (1500 ppm). Cats exhibited signs judged to be indicative of central nervous system depression after a 4-hr inhalation of 49 mg/liter (12,000 ppm) but survived. At the highest concentration obtainable, 180 mg/liter (45,000 ppm), the Lt50 for rats was 4.3 min. Convulsions were produced in about 2 min. Rats and dogs inhaled measured concentrations of 7.9, 3.7, 1.9, and 0.0 mg/liter (2000, 930, 480, and 0.0 ppm) for 6 hr/day, 5 days/wk for 13 wk. The rats tolerated the highest level without any meaningful disturbances in the various criteria of effect that were followed. The only disturbing finding in the dogs was the dosage related granulation nodules found in the lungs. There is no evidence that the nodules were caused by the inhalation of Rubber Solvent but we cannot deny the condition may have been some-what exacerbated by the solvent vapor. This statement is based upon the 4-hr LC50 of 61 mg/liter (15,000 ppm) for rats and the lack of any similar lung pathology in rats that inhaled the same vapor: air mixtures in company with the dogs, for 13 wk. The odor of the solvent is detectable at 0.04 mg/liter (10 ppm) and 15-min periods of inhalation by human subjects resulted in good acceptance of the recommended hygienic standard.

Petroleum hydrocarbon toxicity studies. IX. Animal and human response to vapors of "80 thinner.".

Abstract The suggested hygienic standard for human inhalation of “80 Thinner”, based upon the results of inhalation studies with rats and dogs and the sensory response of human subjects, is 0.45 mg/liter (100 ppm). The LC50 for rats that inhaled “80 Thinner” for 4 hr was 27 (24 to 30) mg/liter or 6200 (5500 to 6900) ppm. Rats tolerated 3.5 mg/liter (810 ppm) and dogs 2.1 mg/liter (480 ppm) for 4 hr without visible discomfort. Four cats that inhaled 24.0 mg/liter (5500 ppm) for 4 hr had signs suggestive of central nervous system effect, became prostrate in 41 to 65 min, but recovered and survived the 14-day observation period. After inhaling a concentration of 1.7 mg/liter (390 ppm) for 6 hr/day, 5 days per week, neither rats nor dogs were statistically significantly different from their controls in any criterion of effect after 14 weeks of inhalation. The oder threshold, as determined by a sniff test involving six human subjects, is approximately 0.004 mg/liter (0.9 ppm). Only slight, transitory eye irritation was reported by one of six human subjects immediately following a 15-min period in 0.45 mg/liter (100 ppm) and variable responses as to comfort at about 1.0 mg/liter (230 ppm). It is anticipated that 0.45 mg/liter (100 ppm) would be tolerable for continuous inhalation in the workroom atmosphere.