Registration Dossier

Administrative data

Description of key information

A number of subacute and subchronic studies with kerosines and jet fuels are available (OECD 410, 412, 413, and other non-guideline protocols). The repeated inhalation and oral studies of kerosine in rats produced no consistent toxicological effects other than changes in male rat kidneys that are not considered relevant to humans. The NOAEC for inhalation exposure is greater than or equal to 1000 mg/m3 (vapour).  The systemic dermal NOAEL is greater than or equal to 0.5 mL/kg/day (400 mg/kg bw/day).  The NOAEL for systemic effects of oral exposure is 750 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
750 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
1 000 mg/m³

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
400 mg/kg bw/day

Additional information

A number of subacute and subchronic studies with kerosines and jet fuels are available. The repeated inhalation and oral studies of kerosine in rats produced no consistent toxicological effects other than changes in male rat kidneys that are not considered relevant to humans. The male-rat specific nephropathy, evident at exposures from 500 mg/m3(inhalation), or 750 mg/kg/day (oral gavage) is not taken into account for risk assessment purposes. The nephropathy in inhalation studies coincided with a decreased bodyweight gain in male rats. No other signs of toxicity were observed. The NOAEC for inhalation exposure is greater than or equal to 1000 mg/m3 (vapour). The systemic dermal NOAEL is greater than or equal to 0.5 mL/kg/day (400 mg/kg bw/day). The NOAEL for systemic effects of oral exposure is 750 mg/kg/day.

 

Oral Exposure

In the key oral subchronic study (Klimisch score=1; Mattie et al., 2000), male rats were treated for 70 to 90 days with 0 (1mL of distilled water), 750, 1500, or 3000 mg/kg/day of undiluted JP-8 jet fuel, then mated to untreated females (one female at a time). Males were gavaged throughout the cohabitation period and were returned to their individual cage after successful mating. In the second part of the study, female rats were administered the test compound at doses of 0 (1mL of distilled water), 375, 750, or 1500 mg/kg/day undiluted JP-8 jet fuel for 90-day prior to mating, through mating, gestation, delivery, and lactation for a total of 21 week. During mating, they were housed with untreated males. 

 

There were no effects on clinical signs or mortality in either sex. Haematology, clinical chemistry, and urinalysis were measured only in females without any effects noted. Body weights in male rats were decreased in a dose-dependent manner and was likely related to nephropathy, which is specific in male rats treated with hydrocarbons, and not relevant for human exposure. In females, body weight was only significantly reduced in the high-dose group. Absolute and relative liver weights were increased in mid- and high-dose females, but were not likely biologically significant due to the lack of changes in clinical chemistry or histopathology in the liver. The test compound caused perianal dermatitis (high-dose only) and stomach hyperplasia (mid- and high-dose) in the female rats. There was a dose-related decrease in pup weight that was significant in the 750 mg/kg/day group on postnatal day 4 only and in the 1500 mg/kg/day group from postnatal day 4 through postnatal day 21 but had recovered by postnatal day 90. There were no treatment-related effects on reproduction or sperm parameters in males. There were no effects on reproduction, gestation, or litter size in females.

 

The study LOAEL for systemic effects is 1500 mg/kg/day and the NOAEL for systemic effects is 750 mg/kg/day, based on reduced body weight in dams and in pups. The LOAEL for adult males rats exposed to JP-8 orally was 750 mg/kg/day due to changes in clinical pathology, body weight, organ weights and the same irritation seen in female rats. The decrease in male rat bodyweight is very likely due to the male rat-specific nephropathy and is therefore not taken into account for the derivation of the oral NOAEL. The reproduction NOAEL was 3000 and 1500 mg/kg/day in males and females, respectively. 

 

Inhalation Exposure

In a key subacute inhalation toxicity study (Klimisch score = 1; API, 1986), hydrodesulfurised kerosine vapour was administered to 20 Sprague-Dawley rats/sex/concentration by dynamic whole body exposure at a concentration of 24 mg/m3(0.024 mg/L) for 6 hours per day, 5 days/week for 4 weeks. There were no compound related effects in mortality, clinical signs, body weight, haematology, clinical chemistry, organ weights, or gross and histologic pathology.  Therefore, the NOAEC is greater than or equal to 24 mg/m3. This was the highest dose tested in the study.

 

In the key subchronic inhalation toxicity study (Klimisch score=1; Mattie et al., 1991), JP-8 jet fuel was administered to 95 male Fisher 344 rats, 75 female Fischer 344 rats, and 100 male and female C57BL/6 mice by dynamic whole body vapour exposure at concentrations of 0, 500 or 1000 mg/m3(0, 0.5, or 1.0 mg/L) as a vapour for 24 hours per day, 7 days/week for a total of 90 days. The male rats developed hydrocarbon-induced nephropathy at both treatment concentrations. Male rats had decreased body weight and decreased absolute and relative kidney weight at both treatment concentrations.  Female rats were unaffected by treatment. In mice, no significant clinical signs of toxicity were noted that differentiated the groups that were treatment-related. The NOAEC for male rats is difficult to establish, since potential adverse effects may be masked by male rat specific hydrocarbon nephropathy. However, based on the hydrocarbon-induced nephropathy and reduced body weights and increased kidney weights, the LOAEC in male rats is 500 mg/m3. The LOEC for male mice is also 500 mg/m3, but it was not treatment related. The NOAEC for female rats and mice is greater than or equal to 1000 mg/m3.  This was the highest dose tested in the study.

 

Dermal Exposure

In the key short-term dermal toxicity study (Klimisch = 1; ARCO, 1992v), thermocracked kerosine was applied to the shaved skin of 10 Sprague-Dawley rats/sex/dose at dose levels of 0, 0.01, 0.05, or 0.5 mL/kg bw/day, 6 hours/day for 5 days/week during a 28-day period. The test compound irritated the skin in a dose-dependent manner. In the high-dose group, the irritation became severe so the application site was moved to a cephalad location at the beginning of the fourth week. There were no compound related effects in mortality, clinical signs, body weight, haematology, clinical chemistry, organ weights, or gross and histologic pathology (except the skin). The LOAEL for dermal irritation is 0.01 mL/kg/day, based on slight to severe dermal irritation occurring at all doses tested. No dermal irritation NOAEL was established. There was no systemic LOAEL, based on the lack of systemic effects. The systemic NOAEL is greater than or equal to 0.5 mL/kg/day. This was the highest dose tested in the study.

 

In supporting short-term dermal studies (ARCO, 1993; ARCO, 1992w; ARCO, 1992x;), groups of male and female young adult Sprague-Dawley rats were administered undiluted straight run kerosine at doses of 0.01, 0.10 or 1.0 mL/kg bw/day (ARCO, 1993), Jet Fuel A1 at doses of 0.01, 0.05 or 0.25 mL/kg bw/day (ARCO, 1992), straight run kerosine at doses of 0.01, 0.25 or 0.5 mL/kg bw/day (ARCO, 1992x), or kerosine/heating oil, Jet Fuel A, Cherry Point Jet Fuel, and JP-5 at doses of 0.5, 2.0 and 5.0 mL/kg/day (ARCO, 1987j; ARCO, 1987k; ARCO, 1987l; ARCO, 1987m). The test material was applied to the previously shorn skin and was occluded for a 6 hour period five days a week for four weeks. There were no mortalities during the studies.  Skin irritation ranged from slight to severe and was typically dose-related. The systemic NOAELs ranged from 0.25 to 2.0 mL/kg/day. The LOAELs for dermal irritation ranged from 0.01 to 0.5 mL/kg/day.

 

In another supporting short-term dermal study (API, 1985b), undiluted test material straight run kerosine was applied to the shorn dorsal skin of each of five male and five female rabbits at doses of 200, 1000 and 2000 mg/kg/day, three times weekly until 12 doses had been applied. Five rabbits of each sex served as sham treated controls. Dosing was carried out on alternate days. The test compound caused skin irritation at all doses with effects of body weight, organ weight, haematology, and histopathology likely secondary to the dermal irritation. Therefore, the LOAEL is 200 mg/kg/day.

Summary

A NOAEC for inhalation exposure of greater than or equal to 1000 mg/m3(vapour) was established. Considering an average breathing rate for female rats of 0.182 m3/day and the average female rat bodyweight of 0.258 kg, the NOAEC of greater than or equal to 1000 mg/m3corresponds with a calculated NOAEL of greater than or equal to 705 mg/kg/day. This is well in agreement with the experimentally determined oral NOAEL of 750 mg/kg/day for female rats.  The repeat dose toxicity of kerosine is not classified using EU CLP Regulation (EC No. 1272/2008).

 

Additional data support that kerosines are not classified as harmful to health after prolonged exposure (inhalation:Carpenter et al., 1976; Shell, 1979; dermal: API, 1980a; API, 1983b; Freeman et al., 1990; CONCAWE, 1991; CONCAWE 1993; Batelle, 1997). This information is presented in the dossier.

 


Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Justification for classification or non-classification

Based on the lack of adverse systemic effects even with the highest doses administered, kerosines are not classified under the EU CLP Regulation (EC No. 1272/2008).