Butanal, reaction products with aniline

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

There is no fertility study with butanal, reaction products with aniline available.

Repeated dose toxicity: No evidence of toxicity to reproductive was observed in a subacute repeated dose study as no treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination. On the basis of this study no effects on fertility were expected (NOAEL, rat: 400 mg/kg bw/day).

Screening study:

According to  Regulation (EC) No 1907/2006 Annex VIII 8.7.1 a screening for reproductive/developmental toxicity, one species (OECD 421 or 422) is required, if there is no evidence from available information on structurally related substances, from (Q)SAR estimates or from in vitro methods that the substance may be a developmental toxicant.

The substance used to be registered in the tonnage band 100-1000 t and a testing proposal for a developmental toxicity study according to OECD 414 had been included in a testing proposal.  With the reduction of the tonnage band to 10-100 t the OECD 414 is no longer needed.

A screening study according OECD TG 421 is therefore planned

 

 

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Short description of key information:
There was no fertility study with butanal, reaction products with aniline available. No effects on reproductive organs were observed in a 28 day study in rats. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epidiymides, prostate, seminal vesicle coagulation gland, ovaries, and uterus. No treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination of all major organs (NOAEL, rat: 400 mg/kg bw/day; males and females).

Effects on developmental toxicity

Description of key information

A study according OECD TG 421 is planned

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available (further information necessary)

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Toxicity to reproduction: other studies

Description of key information

Butanal, Reaction Products with Aniline was administered by gavage to 5 male and 5 female Wistar (HsdRCCHan) rats per dose group in daily doses of 0, 25, 100 or 400 mg/kg body weight for a period of at least 32 days. The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical pathology of blood samples was performed. Functional observational battery (FOB) and motor and locomotor activity measurements (MA/LMA) were done. At the end of the treatment period all animals were killed and a gross and microscopic examination of all major organs, including reproductive organs was conducted. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epidiymides, prostate, semical vesicle coagulation gland, ovaries, and uterus.

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline No. 407

Principles of method if other than guideline:

Butanal, Reaction Products with Aniline was administered by gavage to 5 male and 5 female Wistar (HsdRCCHan) rats per dose group in daily doses of 0, 25, 100 or 400 mg/kg body weight for a period of at least 32 days. The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical pathology of blood samples was performed. Functional observational battery (FOB) and motor and locomotor activity measurements (MA/LMA) were done. At the end of the treatment period all animals were killed and a gross and microscopic examination of all major organs, including reproductive organs was conducted. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epidiymides, prostate, seminal vesicle coagulation gland, ovaries, and uterus.

GLP compliance:

yes

Type of method:

in vivo

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

At least 32 days

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
0, 25, 100 or 400 mg/kg body weight
Basis:
other: nominal

No. of animals per sex per dose:

5 male and 5 female rats/dose

Control animals:

yes, concurrent vehicle

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

other:

Remarks:

No evidence of toxicity to reproductive was observed in a subacute repeated dose study as no treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination. On the basis of this study no effects on fertility were expected (NOAEL, rat: 400 mg/kg bw/day).

There were no test substance-related toxic changes in organs weights of testes, epididymides, prostate, semical vesicle coagulation gland, ovaries, and uterus. No histopathological changes were found in testis, epididymides, prostate, seminal vesicle coagulation gland, ovaries and uterus.

Conclusions:

No evidence of toxicity to reproductive was observed in a subacute repeated dose study as no treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination. On the basis of this study no effects on fertility were expected (NOAEL, rat: 400 mg/kg bw/day).

Executive summary:

Butanal, Reaction Products with Aniline was administered by gavage to 5 male and 5 female Wistar (HsdRCCHan) rats per dose group in daily doses of 0, 25, 100 or 400 mg/kg body weight for a period of at least 32 days. The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical pathology of blood samples was performed. Functional observational battery (FOB) and motor and locomotor activity measurements (MA/LMA) were done. At the end of the treatment period all animals were killed and a gross and microscopic examination of all major organs, including reproductive organs was conducted. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epidiymides, prostate, semical vesicle coagulation gland, ovaries, and uterus.

No evidence of toxicity to reproductive was observed in a subacute repeated dose study as no treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination. On the basis of this study no effects on fertility were expected (NOAEL, rat: 400 mg/kg bw/day).

Additional information

No effects on reproductive organs were observed in a 28 day study in rats. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epidiymides, prostate, semical vesicle coagulation gland, ovaries, and uterus. No treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination of all major organs (NOAEL, rat: 400 mg/kg bw/day; males and females).

There were no test substance-related toxic changes in organs weights of testes, epididymides, prostate, seminal vesicle coagulation gland, ovaries, and uterus. No histopathological changes were found in testis, epididymides, prostate, seminal vesicle coagulation gland, ovaries and uterus.

Justification for classification or non-classification

There are no studies for toxicity to reproduction and/or developmental toxicity available.

A screening OECD TG 421 is therefore planned.

A classification/non-classifiation according to CLP classification criteria (Regulation (EC) No 1272/2008) will be done after the availability of the screening toxicity study (OECD TG 421).