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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
other: early study on fertility
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study pre-dates OECD guidelines, but full paper contains some details of study design.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Researches on the toxicity of benzoic aldehyde [Cercetări cu privire la toxicitatea aldehidei benzoice]
Author:
Sporn A. et al.
Year:
1967
Bibliographic source:
Igiena 16(1), 23-24
Reference Type:
publication
Title:
SIDS Initial Assessment Report for 13th SIAM (Bern, 7th – 9th November 2001) on Benzoates: Benzoic acid, Sodium benzoate, Potassium benzoate, Benzyl alcohol, CAS Nos. 65-85-0, 532-32-1, 582-25-2, and 100-51-6
Author:
OECD
Year:
2004
Bibliographic source:
http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?key=9d081a2b-4582-464a-99d7-27749e8b324a&idx=0

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study Description from OECD SIDS document for Benzoates:

"A single study was conducted to examine the potential reproductive toxicity of benzaldehyde , and the report was available as a translation from Romanian. A group of 10 rats of breeding age were given 2 mg benzaldehyde in oil (type not specified) by gavage every other day for 32 weeks, equivalent to about 5 mg/kg bw per day. Ten controls were used. Two pregnancies in each rat, one at 75 days and one at 180 days, were studied. The end-points examined included the number of pregnant females, number of offspring born, pup body weight at days 7 and 21 post partum, and pup viability.

At the end of treatment, the body weights of control and treated rats were similar: 265 g and 260 g, respectively. It was reported that fewer females in the group given benzaldehyde than in the control group became pregnant; however, no data or statistical analyses were presented. The authors concluded that treatment did not significantly modify any of the parameters studied. No further details were available.

The NOAEL was about 5 mg/kg bw per day."

This description was confirmed against the original paper, now attached to this endpoint study record.
GLP compliance:
no
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzaldehyde
EC Number:
202-860-4
EC Name:
Benzaldehyde
Cas Number:
100-52-7
Molecular formula:
C7H6O
IUPAC Name:
benzaldehyde
Details on test material:
No data given
Specific details on test material used for the study:
No details given on source or purity of test material.

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
No details given.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: oil, exact type not specified
Details on exposure:
The paper describes exposure as follows: "The animals received a farm ration and once every two days 0.1 ml of oil containing 2 mg of benzoic aldehyde." It is assumed that because the dosing it described as "per os", and the delivery of food is described as a separate event, that the dosing was by gavage, and not a feeding study.
Details on mating procedure:
There are no details in the paper. However, based on the description that each dam was followed through two pregnancy cycles, the animals were most likely co-habitated throughout the study in mating pairs.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
The study describes parturition at 75 days and 180 days, and then describes animal weights at 233 days. This appears to have been the basis of the estimate in the OECD description of 32 weeks.
Frequency of treatment:
Once every two days.
Details on study schedule:
Exposure assumed to begin at cohabitation, and animals monitored throughout the course of the 233 days.
Doses / concentrations
Dose / conc.:
5 mg/kg bw/day (actual dose received)
Remarks:
2 mg substance every other day
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
Study Description from OECD SIDS document for Benzoates:

"A single study was conducted to examine the potential reproductive toxicity of benzaldehyde , and the report was available as a translation from Romanian. A group of 10 rats of breeding age were given 2 mg benzaldehyde in oil (type not specified) by gavage every other day for 32 weeks, equivalent to about 5 mg/kg bw per day. Ten controls were used. Two pregnancies in each rat, one at 75 days and one at 180 days, were studied. The end-points examined included the number of pregnant females, number of offspring born, pup body weight at days 7 and 21 post partum, and pup viability.

At the end of treatment, the body weights of control and treated rats were similar: 265 g and 260 g, respectively. It was reported that fewer females in the group given benzaldehyde than in the control group became pregnant; however, no data or statistical analyses were presented. The authors concluded that treatment did not significantly modify any of the parameters studied. No further details were available.

The NOAEL was about 5 mg/kg bw per day."

This description was confirmed against the original paper, now attached to this endpoint study record.
Positive control:
None stated

Examinations

Parental animals: Observations and examinations:
Two pregnancies per rat were studied, one at 75 days and one at 180 days. The number of pregnant females was examined.
Oestrous cyclicity (parental animals):
Not described.
Sperm parameters (parental animals):
Not described.
Litter observations:
The parameters examined included the number of offspring born, pup body weights at days 7 and 21 postpartum, and pup vitality.
Postmortem examinations (parental animals):
Not described.
Postmortem examinations (offspring):
Not described.
Statistics:
Paper concludes "From the data on subacute and chronic toxicity it appears that in the doses used benzoic aldehyde did not produce significant changes in any of the indicators used," but statistical methods are not described.
Reproductive indices:
Number of pregnant females.
Offspring viability indices:
- Number of pups born
- Pup weight at birth, 7 and 21 days
- Pup viability throughout

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Description (incidence):
Although not explicityl stated, assumption is that given the conclusion that benzaldehyde "did not produce significant changes in any of the indicators used", that no mortality was observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No difference was observed between the average weights of the control and treated groups, when evaluated at 223 days after initation of treatment.
Description (incidence and severity):
N/A, as this was not a feeding study.
Description (incidence and severity):
N/A, as this was not a feeding study.
Description (incidence and severity):
N/A, as this was not a drinking water study.
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Description (incidence and severity):
The paper describes minimal clinical biochemistry for the sub-acute studies described in the paper, but does not describe this for the chronic studies (which included reproduction).
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Description (incidence and severity):
From a gross evaluation, the lack of difference in the reproductive indices evaluated suggests that there was no impact on estrous cycle.
Reproductive function: sperm measures:
not specified
Description (incidence and severity):
From a gross evaluation, the lack of difference in the reproductive indices evaluated suggests that there was no impact on sperm measures.
Reproductive performance:
no effects observed

Details on results (P0)

The number of pregnant females was lower in the group receiving benzoic aldehyde than in the control group, however no detail is given around this observation. The overall conclusion of the paper was that there was no significant changes between the control and treated groups, therefore the decrease in the number of pregnant females can be assumed to not be statistically significant.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
ca. 5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No indications for effects on fertility at limit dose; reference: OECD risk assessment, 2004
Remarks on result:
other: Generation: P and F (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Description (incidence and severity):
Although there is no specific detail, "pup viability" can be assumed to represent clinical signs. There were no differences observed in viability between pups from the control and treated groups.
Mortality / viability:
no mortality observed
Description (incidence and severity):
Although not explicityl stated, assumption is that given the conclusion that benzaldehyde "did not produce significant changes in any of the indicators used", that no mortality was observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant difference between pups from control and treated parental pairs at birth, 7 or 21 days post partum.
Food efficiency:
not specified
Description (incidence and severity):
N/A, as this was not a feeding study.
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
N/A, as this was not a drinking water study.
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

No statistical difference in observations between F1 generations from control and treated F0 generation.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Reproductive Toxicity

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
In the one-generation reproduction study in rats, it was concluded that treatment did not affect reproduction (limited study design and reporting).
Executive summary:

Cited from OECD 2004: "A single study was conducted to examine the potential reproductive toxicity of benzaldehyde, and the report was available as a translation from Romanian. A group of 10 rats of breeding age were given 2 mg benzaldehyde in oil (type not specified) by gavage every other day for 32 weeks, equivalent to about 5 mg/kg bw per day. Ten controls were used. Two pregnancies in each rat, one at 75 days and one at 180 days, were studied. The end-points examined included the number of pregnant females, number of offspring born, pup body weight at days 7 and 21 post partum, and pup viability.

 

At the end of treatment, the body weights of control and treated rats were similar: 265 g and 260 g, respectively. It was reported that fewer females in the group given benzaldehyde than in the control group became pregnant; however, no data or statistical analyses were presented. The authors concluded that treatment did not significantly modify any of the parameters studied. No further details were available. The NOAEL was about 5 mg/kg bw per day."

 

(Sporn et al. 1967, OECD 2004)