1,6-dichlorohexane

Endpoint summary

Description of key information

A reproduction/developmental toxicity screening test was performed with 1,6-dichlorohexane according to OECD guideline no. 421.
The following no-observed-effect levels (NOAEL) of the test item were noted:
The NOAEL (no-observed-adverse-effect level) on the F0-generation was 210 mg/kg bw/day, p.o..

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

210 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP study
OECD guideline was followed (Klimisch 1).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A reproduction/developmental toxicity screening test was performed with 1,6-dichlorohexane in 80 rats (in four groups) according to OECD guideline no. 421. The vehicle is corn oil. The test item was administered orally to rats at dose levels of 70, 210 and 630 mg/kg bw/day during the pre-mating, mating and post-mating periods to parental males as well as during the pre-mating, mating, gestation and lactation periods until day 3 post-partum to parental female animals.

At 210 mg 1,6-dichlorohexane/kg bw/day, reduced motility, piloerection and/or slightly or moderately increased salivation were temporarily noted in a few male or female rats. In addition, reductions were noted for body weight and food consumption.

Treatment with 630 mg 1,6-dichlorohexane/kg bw/day caused - in relation to the dose - more distinct signs of toxicity in the form of reduced motility, ptosis and increased salivation in several to all rats of both sexes, piloerection, ataxia or increased drinking water consumption in one or few male or female animals as well as reduced body weight and food intake.

None of the parental animals died prematurely. Macroscopic inspection did not reveal any test item-related changes at necropsy.

No test item-related changes were noted for the weights of the testes and epididymides. Histopathological examination of the reproduction organs did not reveal any test item-related changes. No test item-related influence was noted on the qualitative sperm staging.

No test item-related influence was noted on mating behaviour, fertility, implantation, the gestation length or the birth index up to a dose level of 210 mg 1,6 -dichlorohexane/kg bw/day.

At the materno-toxic dose level of 630 mg 1,6-dichlorohexane/kg bw/day, a slightly increased post-implantation loss and a statistically significantly reduced live birth index were noted due to an increased incidence of stillbirths.

No test item-related influence was noted up to a dose level of 70 mg 1,6 -dichlorohexane/kg bw/day on the growth and development of the offspring from conception until sacrifice on day 4 post-partum.

From a dose level of 210 mg 1,6 -dichlorohexane/kg bw/day onwards, a dose-dependent reduction was noted for the body weight of pups.

An adverse effect on the development of the pups was noted at the materno-toxic dose level of 630 mg 1,6 -dichlorohexane/kg bw/day, indicated by a reduced mean and total litter weight and a reduced survival rate of the pups.

The NOAEL (no-observed-adverse-effect level) on the F0-generation was 210 mg/kg bw/day, p.o..

The NOAEL (no-observed-adverse-effect level) of reproductive toxicity was 210 mg/kg bw/day, p.o..

The NOAEL (no-observed-adverse-effect level) of the F1 offspring (pups) was 70 mg/kg bw/day, p.o.

 

Discussion:

Neurotoxicological effects were observed in male and female animals of the high dose group, which might be associated with n-hexane, a structural analogue of 1,6-dichlorohexane. However, since the derived DNEL for 1,6-dichlorohexane is well below the MAK value of n-hexane (180 mg/m³) and exposure is estimated to be low the derived inhalation DNEL (long-term, systemic) is considered to ensure an appropriate level of protection with regard to neurotoxicological effects. Therefore, no further neurotoxicological study is required.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one key study is available.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after inhalation does not need to be conducted as repeated dose toxicity studies for oral application are available or will be proposed.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after inhalation does not need to be conducted as repeated dose toxicity studies for oral application are available or will be proposed.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after dermal application does not need to be conducted as repeated dose toxicity studies for oral application are available or will be proposed.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after dermal application does not need to be conducted as repeated dose toxicity studies for oral application are available or will be proposed.

Justification for classification or non-classification

Based on the results of the subacute oral toxicity study, the test substance should not be subject to classification for repeated dose or specific target organ toxicity according to the criteria of EU Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.