2-benzylideneheptanal

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction via oral route

The no observed adverse effect level (NOAEL) for maternal toxicity was considered to be 510.97 mg/kg bw/day.When rats were treated with  2-benzylideneheptanal (122-40-7) orally.

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Prediction is done using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: refer below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-benzylideneheptanal
- Molecular formula: C14H18O
- Molecular weight : 202.2952 g/mole
- Substance type: Organic
- Physical state:Liquid

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: unspecified

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Premating exposure period: 14 d
Total exposure period: males 47 d, females 46 d.

Frequency of treatment:

Daily

Dose / conc.:

510.97 mg/kg bw/day

No. of animals per sex per dose:

25

Control animals:

not specified

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

Postmortem examinations (parental animals):

GROSS NECROPSY: Yes

HISTOPATHOLOGY / ORGAN WEIGHTS: Yes

Clinical signs:

no effects observed

Description (incidence and severity):

No test substance related effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No test substance related effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

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:

no effects observed

Description (incidence and severity):

No test substance related effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

no effects observed

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

No test substance related effects observed

Dose descriptor:

NOAEL

Effect level:

510.97 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

clinical signs

body weight and weight gain

histopathology: non-neoplastic

reproductive performance

other: No effects observed.

Remarks on result:

other: No effect was observed

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Remarks on result:

not measured/tested

Critical effects observed:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

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

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Remarks on result:

not measured/tested

Critical effects observed:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

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

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Remarks on result:

not measured/tested

Critical effects observed:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" or "e" )  or "f" or "g" )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aldehydes (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds AND AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes AND AN2 >> Schiff base formation AND AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> alpha-alkyl cinnamaldehyde derivatives by DPRA Cysteine peptide depletion ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR Michael addition OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds >> alpha,beta-Aldehydes  OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls by Protein binding by OECD ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Aldehydes by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Aldehydes by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aldehydes by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 13 - Metals Al,Ga,In,Tl by Chemical elements

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.67

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.37

Conclusions:

The no observed adverse effect level (NOAEL) for maternal toxicity was considered to be 510.97 mg/kg bw/day.When rats were treated with 2-benzylideneheptanal (122-40-7) orally.

Executive summary:

The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.4 (2017); to evaluate the toxic effects of administration of 2-benzylidenehepta nal (CAS No. 122-40-7) in rat by the oral route. No effects observed on clinical signs, body weight, gross pathology and histopathology. Hence the no observed adverse effect level (NOAEL) for maternal toxicity was considered to be 510.97 mg/kg bw/day.When rats were treated with  2-benzylideneheptanal (122-40-7) orally.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

510.97 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The data is Klimicsh 2 and from OECD QSAR toolbox version 3.4 (2017).

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to reproduction via oral route

Various studies including predicted results from the validated model and experimental study has been investigated for reproductive toxicity to a greater or lesser extent for the test chemical 2-benzylideneheptanal (CAS No. 122-40-7) along with its structurally similar read across substance α-hexylcinnamaldehyde (CAS No. 101 -86 -0) and 2-(4-tert-butylbenzyl) propionaldehyde) (CAS No. 80-54-6).The predicted data for target chemical 2-benzylidenehepta nal (CAS No. 122-40-7) has been compared with experimental study for a read across substance. The studies are summarized as below:

 

The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.4 (2017); to evaluate the toxic effects of administration of 2-benzylidenehepta nal (CAS No. 122-40-7) in rat by the oral route. No effects observed on clinical signs, body weight, gross pathology and histopathology. Hence the no observed adverse effect level (NOAEL) for maternal toxicity was considered to be 510.97 mg/kg bw/day.When rats were treated with  2-benzylideneheptanal (122-40-7) orally. 

This is further supported by the one generation study published in a report of (Human Health Tier II Assessment For Amyl and hexyl cinnamaldehy de (2017))on structurally similar read across substance α-hexylcinnamaldehyde (CAS No.-101-86-0).In a one generation study conducted similarly to OECD TG 421, Crj: CD (SD) rats (eight animals/sex/dose) were fed α-hexylcinnamaldehyde (CAS No.-101-86-0) in corn oil at 12.5, 25, 50 or 1000 mg/kg bw. The males received the treatment for 14 days before cohabitation,through mating for a maximum of seven days and were euthanised on the day 47 of treatment. Female rats were treated two weeks before cohabitation, through mating and were euthanised on day 45 of treatment. The first group of offspring (FI) generation pups were euthanised on fifth day of lactation. No treatment related clinical observations or gross lesions were seen in the parent (P) generation of either sex. Body weights and feed consumption were unaffected in male rats. In treated P generation female rats, the body weights or body weight gains and the feed consumption were not affected by the treatment during the pre cohabitation and the gestation periods. A significant decrease in maternal body weight in the 1000 mg/kg bw/day dose group was reported during the lactation period and was considered as the maximum tolerated dose (MTD). No treatment related effect was seen on oestrous cycling, mating and fertility at any tested dose. No treatment related clinical or necropsy effects were seen in the F1 generation pups and no developmental effects were observed. Hence The NOAEL for maternal and developmental toxicity was considered to be  >=1000 mg/kg bw/day. When rats were treated with α-hexylcinnamaldehyde (CAS No.-101-86-0) orally. 

 

The above study is supported by the experimental study by A.M. Api et al. (Food and Chemical Toxicology Volume 82, Supplement, August 2015, Pages S20-S28), on structurally similar read across substance α-hexylcinnamaldehyde (CAS No.-101-86-0). The study was designed to investigate the reproductive toxicity effects of α-hexylcinnamaldehyde (CAS No.- 101-86-0) in rats by the oral route. No effects were observed on mating, fertility, reproductive organ weights, reproductive organ microscopic examination,delivery parameters, pup body weights, and pup clinical and necropsy observations. There were non-significant decreases in maternal body weight gain and feed consumption during lactation. hence the NOAEL for reproductive and developmental  toxicity was considered to be 100 mg/kg/day, the highest dosage tested.When rats were treated with α-hexylcinnamaldehyde (CAS No.- 101-86-0) orally 

Moreover, in the study published in a U.S. Environmental Protection Agency Risk-Based Prioritization Document (Initial Risk-Based Prioritization of High Production Volume (HPV) Chemicals Cinnamyl Derivatives Category), on structurally similar read across substance p-t-Butyl-alpha-methylhydrocinnamaldehyde (2-(4-tert-butylbenzyl) propionaldehyde) (CAS No.80-54-6).The study was designed to investigate the reproductive toxicity effects of p-t-Butyl-alpha-methylhydrocinnamaldehyde (2-(4-tert-butylbenzyl) propionaldehyde) (CAS No.80-54-6) in dogs by the oral route. Beagle dogs (6/sex/dose) were administered p-t-butyl-alpha-methylhydrocinnamaldehyde orally via gelatin capsules at 4.4, 22.3 and 44.6 mg/kg-bw/day for 91 days. No adverse effects on body weight, behavior, haematological, clinical parameters or histopathology were observed at any dose. Histological evaluation was performed on the male and female reproductive organs from each dose group and the control group. In the high dose males, the presence of spermatoceles and testicular atrophy were seen. No treatment-related effects on the female reproductive system were observed. Hence NOAEL was considered to be for male dogs  = 22.3 mg/kg bw/day and female dogs = 44.6 mg/kg bw/day.When Beagle dogs were treated with  p-t-Butyl-alpha-methylhydrocinnamaldehyde (2-(4-tert-butylbenzyl) propionaldehyde) (CAS No.80-54-6) orally. 

So, based on the above mentioned studies for target substance 2-benzylideneheptanal (CAS No. 122-40-7) and to its read across substance, it was considered that no adverse effects on sexual function and fertility was observed. Therefore, according to CLP criteria, the substance 2-benzylidene heptanal (CAS No. 122-40-7) cannot be classified as reproductive toxicant.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation2-benzylideneheptanal (CAS No. 122-40-7) can be "Not classified" for reproductive toxicity.