Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

This endpoint is not a REACH requirement.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 500 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
supported by screening studies
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
1 000 mg/m³
Study duration:
subchronic
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
494 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Additional information

The animal data indicate that long-term oral or inhalation exposure to jet fuels and kerosines has no effect on the fertility of male rats up to a dose of 3000 mg/kg/day or a concentration of 1000 mg/m3 (highest concentration tested) and no effect on the fertility of female rats up to a dose of 1500 mg/kg/day (highest concentration tested). Although one study showed an altered expression of some testis proteins, this cannot directly be related to reproductive malfunctioning.

 

In a sub-chronic oral test, reproductive toxicity screening was performed (Mattie et al., 2000). Males 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). In the second part of the study, female rats were administered the test compound at doses of 0 (1 mL 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 systemic signs of toxicity. There were no treatment-related effects on reproduction or sperm parameters in males. There were no treatment-related effects on reproduction, gestation, or litter size in females. 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. The reproduction NOAEL was greater than or equal to 3000 and greater than or equal to 1500 mg/kg/day in males and females, respectively.

In a reproductive/developmental toxicity screening study (Klimisch score=1; Schreiner et al., 1997), 10 Sprague Dawley rats/sex/group were treated dermally with hydrodesulfurised kerosine at concentrations of 0 (sham-treated and vehicle control groups), 165, 330 or 494 mg/kg/day (0, 20, 40 or 60% (v/v) respectively) in mineral oil in a dosing volume of 1 mL/kg for a minimum of 6 hours, 7 days/week beginning 14 days premating, during the 14-day mating period and through 20 days of gestation. Rats were mated overnight on a 1:1 ratio and were separated the following morning. Pregnancy was determined by the presence of a vaginal plug or sperm in a vaginal lavage sample. If observed, the female was considered to be at day 0 of gestation. Any female that did not show evidence of mating was placed with the same male the following evening. Any female that did not show evidence of mating at the end of a 2-week mating period was presumed pregnant (gestation day 0 = last day of cohabitation). Skin irritation occurred in both males (all doses) and females (high dose only). At terminal sacrifice, no findings were reported except for those on the skin. Body weights were unaffected by treatment. However over the course of the 8 weeks, high-dose males gained less weight than the controls. Food consumption was unaffected by treatment. High-dose males had a higher mean relative kidney weight than controls (0.76 vs. 0.66). This was attributed to the lower mean final body weights of the high-dose group. No other organ or organ/body weight changes were recorded. No test-material-related microscopic changes were observed in the testes or epididymides of adult male rats or in the ovaries of adult female rats. There is no parental systemic LOAEL, based on the lack of any significant treatment-related findings except dermal irritation. The parental systemic NOAEL is greater than or equal to 494 mg/kg/day. There is no offspring LOAEL, based on the lack of any effects noted in the offspring. The offspring NOAEL is greater than or equal to 494 mg/kg/day.

In a supporting inhalation study, male Sprague-Dawley rats were exposed for 6 hours/day for 91 consecutive days to JP-8 Jet Fuel vapour at concentrations of 0, 250, 500 and 1000 mg/m3 (Witzmann et al., 2003). After exposure the rats were sacrificed and testis were dissected, solubilised, separated and analyzed for expression of testis proteins. During exposure the rats did not exert any overt signs of clinical toxicity. The results of the protein analysis show that in exposed rats several testis proteins were increased and several testis proteins were decreased significantly as compared to the controls. The expression levels of the following proteins showed a dose-related increase: HsP86, nicotinic acetylcholine receptor alpha subunit, serum albumin and T-complex protein 1. However, the increased expression of these proteins cannot directly be related to reproductive malfunctioning. The NOAEC based on these effects is greater than or equal to 1000 mg/m3. 

 

An additional inhalation supporting study was conducted in a similar fashion, which supports these conclusions (Price et al., 2001). 

 

Additional data support that kerosines are not reproductive toxicants (API, 1979c; PPSC, 1995; Schreiner et al., 1997). This information is presented in the dossier.

Short description of key information:

Kerosine does not cause fertility effects in animals following inhalation, dermal and oral exposure  .

Justification for selection of Effect on fertility via oral route:

Reproductive NOEL was 1500 mg/kg/day based on no effects in females receiving this dose. For males the reproductive NOEL was 3000 mg/kg/day

Effects on developmental toxicity

Description of key information

All animal studies show that kerosine and jet fuel have no effects on development (OECD 414). The most important effect in animals following high doses was a decreased body weight of the females and of the pups at 1500 mg/kg/day. The NOAEL for decreased pup weight was 1000 mg/kg/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
364
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

All animal studies show that kerosine and jet fuel have no effects on development. The most important effect in animals following high doses was a decreased body weight of the females and of the pups at 1500 mg/kg/day. The NOAEL for decreased pup weight was 1000 mg/kg/day.

In a key reproductive/developmental toxicity screening study (Klimisch score=1; Schreiner, et al., 1997), 10 Sprague Dawley rats/sex/group were treated dermally with hydrodesulfurised kerosine at concentrations of 0 (sham-treated and vehicle control groups), 165, 330 or 494 mg/kg/day (0, 20, 40 or 60% (v/v), respectively) in mineral oil in a dosing volume of 1 ml/kg for a minimum of 6 hours,7 days/week beginning 14 days premating, during the 14-day mating period and through 20 days of gestation. Dosage equivalents were 0, 165, 330 and 494 mg/kg/day. There is no offspring LOAEL, based on the lack of any effects noted in the offspring. The offspring NOAEL is greater than or equal to 494 mg/kg/day. This was the highest dose tested in the study.

 

In the key developmental toxicity study (Klimisch score=1; Cooper and Mattie, 1996), undiluted JP-8 jet fuel was administered to 30 Sprague-Dawley (Crl:CD) rats/dose by gavage at various volumes to achieve dose levels of 0 (sterile water), 500, 1000, 1500, or 2000 mg/kg bw/day from days 6 through 15 of gestation. There was a significant decrease in foetal weight in both male and female foetuses with 1500 and 2000 mg/kg/day. The test compound did not significantly increase the incidence of malformations or variations compared to the control nor was the sex ratio altered. The developmental LOAEL is 1500 mg/kg/day, based on reduced foetal weight. The developmental NOAEL is 1000 mg/kg/day.

 

In a key pre-natal developmental study (Klimisch score=1; API, 1979b), 20 female presumed-pregnant rats per group were exposed to 106 or 364 ppm kerosine vapour for 6 hours each day on days 6 through 15 of gestation. A control group of 20 presumed-pregnant rats of the same age served as controls and were placed in chambers and exposed to room air only. The animals were sacrificed on day 20 of gestation. There were no effects noted on either the dams or the foetuses. The NOAEC is greater than or equal to 364 ppm, based on the lack of effects and no LOAEC can be determined.

 

Justification for selection of Effect on developmental toxicity: via oral route:

One of three well conducted guideline studies that showed no developmental toxicity

Toxicity to reproduction: other studies

Additional information

This endpoint is not a REACH requirement.

Justification for classification or non-classification

Available data indicate that long-term oral or inhalation exposure to jet fuels and kerosines has no effect on the fertility of male rats up to a dose of 3000 mg/kg/day or a concentration of 1000 mg/m3 (highest concentration tested) and no effect on the fertility of female rats up to a dose of 1500 mg/kg/day (highest concentration tested). Therefore, there is insufficient data to classify kerosines as toxic for reproduction under the EU CLP Regulation (EC No. 1272/2008).

Developmental studies did not provide sufficient evidence to cause a strong suspicion of developmental toxicity in the absence of signs of marked maternal toxicity, therefore kerosines are not classified as a developmental toxicant according to EU CLP Regulation (EC No. 1272/2008).