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Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL was estimated to be 248 mg/kg bw when Wistar male and female rats were orally exposed with Anisoyl chloride.  

Thus, as per criteria of CLP regulation, Anisoyl chloride can be not classified for reproductive toxicity.  

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:
Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- IUPAC Name: 4-Methoxybenzoyl Chloride
- InChI:1S/C8H7ClO2/c1-11-7-4-2-6(3-5-7)8(9)10/h2-5H,1H3
- SMILES:COc1ccc(C(=O)Cl)cc1
- Mol. formula: C8H7ClO2
- Molecular Weight: 170.5943 g/mole
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
polyethylene glycol
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
46 days
Frequency of treatment:
Daily
Details on study schedule:
not specified
Dose / conc.:
248 mg/kg bw/day
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
not specified
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
not specified
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
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
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
Dose descriptor:
NOAEL
Effect level:
248 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
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 / 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
Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
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 8 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acyl chloride OR Acyl halide OR Alkylarylether OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Ether OR Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acyl halide OR Aryl OR Ether OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acyl halide OR Aryl OR Ether by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) by Protein binding by OECD ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AhR binders.Polycyclic aromatic hydrocarbons (PAHs) (3b-3) OR Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acyl chloride AND Acyl halide AND Alkylarylether AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Ether AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.15

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.35

Conclusions:
NOAEL was estimated to be 248 mg/kg bw when Wistar male and female rats were orally exposed with Anisoyl chloride.
Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Anisoyl chloride. The NOAEL was estimated to be 248 mg/kg bw when Wistar male and female rats were orally exposed with Anisoyl chloride.  

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
248 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is Klimisch 2 and from the OECD QSAR toolbox (2018)
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity:

In different studies, Anisoyl chloride has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimation in rodents, i.e. most commonly in rats for Anisoyl chloride along with the study available on structurally similar read across substance 4-methoxybenzaldehyde; Anisaldehyde (CAS no 123-11-5) and 4-methoxyphenylacetic acid (CAS no 104-01-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Anisoyl chloride. The NOAEL was estimated to be 248 mg/kg bw when Wistar male and female rats were orally exposed with Anisoyl chloride.  

In another experimental study given by Organization for Economic Co-operation and Development (Environment Directorate Joint Meeting of the chemicals committee and the working party on chemicals, pesticides and biotechnology Feb 27th, 2012) on structurally similar read across substance 4-methoxybenzaldehyde; Anisaldehyde (CAS no 123-11-5), male and female rats were treated with p-methoxybenzaldehyde in the concentration of 0, 20, 100 and 500 mg/kg bw orally by gavage for approx. 63 days. Epididymidal weight was decreased in males at 500 mg/kg group. The compound showed no adverse effects in terms of estrous cycle, number of corpora lutea and implant rate at any dose level. In the 500 mg/kg bw group, the number of non-pregnant females was increased although all pairs copulated. The delivery index was lower than in controls at 500 mg/kg bw/day. In addition, the number of pups and the number of live pups on lactation day 0 and 4 were lower than in the controls at 500 mg/kg bw/day. No effect on viability of treated rats was observed as compared to control. No effect on body weight of pups observed as compared to control. Therefore, NOAEL was considered to be 100 mg/kg bw for P and F1 generation when male and female rats were treated with p-methoxybenzaldehyde orally by gavage for approx. 63 days.

Further supported by experimental study given by Kotinet al(National Cancer Institute Division of Cancer Cause &Prevention Carcinogenesis Program Bethesda, Maryland, 1968) on structurally similar read across substance 4-methoxyphenylacetic acid (CAS no 104-01-8), B6C3F1 female mice were treated with (4-methoxyphenyl) acetic acid in the concentration of 0 and 215 mg/kg bw/day in 0.5% gelatin for 7 to 28 day and after dose is administer through diet at 560 ppm for 18 months. Body weight gain was observed with the increase in duration of treatment. No gross pathological changes were observed in treated female mice. In addition, no fibroadenoma and carcinoma mammary gland were observed in treated female mice as compared to control. Therefore, NOAEL was considered to be > 215 mg/kg bw when B6C3F1 female mice by using (4-methoxyphenyl) acetic acid for 18 months.

Thus, based on the above study and predictions on Anisoyl chloride and its read across substances, it can be concluded that NOAEL value is 248 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Anisoyl chloride can be not classified for reproductive toxicity.

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

Based on the above study and predictions on Anisoyl chloride and its read across substances, it can be concluded that NOAEL value is 248 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Anisoyl chloride can be not classified for reproductive toxicity.