Anisoyl chloride

Endpoint summary

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

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.