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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The test item does not indicate reproductive/developmental toxicity after repeated dosing in an OECD 422 performed under GLP (data derived from Read-across compound ethyl hexanoate).

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Remarks:
Combined Repeated Dose Toxicity and Reproduction/Developmental Toxicity Screening Test
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2016-08-25 to 2017-02-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study using a read-across test substance
Justification for type of information:
Read-across from ethyl caproate is considered justified based on strong similarities with regards to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles is included in section13 of the IUCLID dossier.
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse treatment-related effects of toxicological significance were observed.
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No treatment-related effects of toxicological significance were observed.
Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Conclusions:
Read-across was performed from ethyl caproate. Based on the result, and on the structural, chemical and toxicological similarities between ethyl caproate and ethyl heptoate, the NOAEL for reproductive/developmental toxicity for ethyl heptoate is greater than 1000 mg/kg bw/day.
Executive summary:

Read-across was performed from ethyl caproate. Potential reproductive/developmental effects of the test item were assessed in rats by oral gavage (12 animals per sex per group) at dose levels of 0, 100, 300 and 1000 mg/kg bw/day dosed for two weeks prior to mating and continued through the day before sacrifice in males (at least 50 days), and continued through the lactation day 13 in females.

The study was performed according to the OECD guideline 422 and in compliance to GLP.

No test item-related change was observed in oestrus cycle, precoital time, fertility data, reproductive and littering findings, F1 pups clinical signs, body weight, anogenital distance, nipple retention and external examinations. Test item-related increase in T4 was observed in adult males (1.14-fold of control) and pups (1.20-fold of control) at 1000 mg/kg bw/day. However, it was not considered to have toxicological relevance since there were no correlated changes in other parameters including microscopic findings of thyroids (with parathyroids).

In conclusion, no test item-related adverse effects for reproductive/developmental effects were observed up to 1000 mg/kg bw/day. Therefore, the No Observed Adverse Effect Level (NOAEL) for reproduction/developmental toxicity is considered to be at least 1000 mg/kg bw/day.

Based on the result, and on the structural, chemical and toxicological similarities between ethyl caproate and ethyl heptoate, the No Observed Adverse Effect Level (NOAEL) for reproductive/developmental effects for ethyl heptoate is considered to be at least 1000 mg/kg bw/day.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 097 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The key study was a good quality study, conducted according to OECD Guideline 422 and complies with GLP: reliable without restrictions. However, these data have been scored as reliability 2: reliable with restrictions when used for read across to the target test substance.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

For this endpoint there is one read-across study available with data on reproductive/developmental toxicity after repeated dosing. This key study is a recent OECD 422 study on the read-across substance ethyl hexanoate performed in compliance with GLP.

In the key study (2017) the read-across substance ethyl hexanoate was tested in a Combined Repeated Dose Toxicity and Reproduction/Developmental Toxicity Screening assay via oral gavage to Sprague-Dawley rats with dose levels of 0, 100, 300 and 1000 mg/kg bw/day.

There were no test item-related adverse effects to the reproductive/developmental system up to 1000 mg/kg bw/day. Therefore, the No Observed Adverse Effect Level (NOAEL) for reproductive/developmental toxicity is considered to be at least 1000 mg/kg bw/day.

Based on the result, and on the structural, chemical and toxicological similarities between ethyl caproate and ethyl heptoate, the NOAEL for ethyl heptoate for reproductive/developmental toxicity can be calculated to be greater than 1097 mg/kg bw/day following molecular weight correction related to the read-across.

Effects on developmental toxicity

Description of key information

In the key combined repeated dose with the reproduction/developmental toxicity screening test in rats (OECD 422), there were no effects of the test item on pup development; therefore, a No Observed Adverse Effect Level (NOAEL) for the test item was 1000 mg/kg bw/day (top dose).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 097 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The key study was a good quality study, conducted according to OECD Guideline 422 and complies with GLP: reliable without restrictions. However, these data have been scored as reliability 2: reliable with restrictions when used for read across to the target test substance.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a key combined repeated dose with the reproduction/developmental toxicity screening test in rats with the test item, no toxicologically-relevant developmental effects were observed. All findings recorded were within the range of normal background alterations.

Justification for classification or non-classification

The read-across substance ethyl caproate did not induce any adverse effects in a reproductive/developmental toxicity screening test in rats.

Based on the results, and on the structural, chemical and toxicological similarities between the read-across substance ethyl caproate and ethyl heptoate, the NOAEL for ethyl heptoate for reproductive/developmental toxicity is greater than 1097 mg/kg bw/day.

According to the criteria set out in the Classification, Labelling and Packaging of Substances and Mixtures Regulation (CLP) No. 1272/2008 in section 3.7 the substance should not be classified. The substance is not toxic to reproduction.

Additional information