Isopropyl 4-hydroxybenzoate

Endpoint summary

Description of key information

LD50 was considered to be > 2000 mg/kg bw when DDY male mice were treated with isopropyl 4-hydroxybenzoate orally.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer-reviewed journal

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute oral toxicity study of isopropyl 4-hydroxybenzoate in mice to set the appropriate dose of each chemical for the comet assay

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Isopropyl Paraben (isopropyl 4-hydroxybenzoate)
- Molecular formula (if other than submission substance): C10H12O3
- Molecular weight (if other than submission substance): 180.202 g/mole
- Substance type: Organic
- Physical state: Solid
Purity >99.0%

Species:

mouse

Strain:

other: DDY

Sex:

male

Details on test animals or test system and environmental conditions:

Source: Japan SLC Co., Shizuoka, Japan
Age at study initiation: 8 weeks
Weight at study initiation: no data available
Fasting period before study: no data available
Housing: no data available
Diet (e.g. ad libitum): commercial pellets MF (Oriental Yeast Industries Co., Tokyo, Japan), ad libitum
Water (e.g. ad libitum): Tap Water, ad libitum
Acclimation period: 1 week of acclimatization

ENVIRONMENTAL CONDITIONS
Temperature (°C): The animal room was at 20–24°C
Humidity (%): No data
Air changes (per hr): No data
Photoperiod (hrs dark / hrs light): 12 h light–dark cycle.

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

Details on exposure
VEHICLE
- Concentration in vehicle: 2000 mg/kg bw
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle:olive oil
- Lot/batch no. (if required):No data available
- Purity:No data available

MAXIMUM DOSE VOLUME APPLIED: No data available

DOSAGE PREPARATION (if unusual): Dose were prepared in olive oil

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In order to set the appropriate dose of each chemical for the comet assay, 0.5 × LD50 or the limit dose of 2000 mg/kg were given to mice.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

4-5 male mice

Control animals:

not specified

Details on study design:

- Other examinations performed: Mortality were observed.

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality observed

Mortality:

No mortality was observed in treated male mice at 2000 mg/kg bw

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Test chemical	Vehicle	Source*	LD50** mg/kg
p-Hydroxybenzoic acid iso-propyl ester	Olive oil	T	>2000

*T = Tokyo Kasei Kogyo Industry Ltd., Tokyo, Japan;

** In order to set appropriate doses for the assay, we determined approximate LD50 by simple acute toxicity experiments on four–five animals. When no death was observed at 2000 mg/kg, the LD50 was defined as >2000 mg/kg.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was considered to be > 2000 mg/kg bw when DDY male mice were treated with isopropyl 4-hydroxybenzoate orally.

Executive summary:

In a acute oral toxicity study, DDY male mice were treated with isopropyl 4-hydroxybenzoate in the limit dose of 2000 mg/kg bw orally in Olive Oil. No mortality was observed in treated male mice at 2000 mg/kg bw. Therefore, LD50 was considered to be > 2000 mg/kg bw when DDY male mice were treated with isopropyl 4-hydroxybenzoate orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from peer-reviewed journal

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, isopropyl 4-hydroxybenzoatehas been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in mice and rats for isopropyl 4-hydroxybenzoate along with the study available on structurally similar read across substance Butylparaben (CAS no 94-26-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

 In a experimental study conducted by Sasaki et al (Mutation Research 519 (2002) 103–119), DDY male mice were treated with isopropyl 4-hydroxybenzoate in the limit dose of 2000 mg/kg bw orally in Olive Oil. No mortality was observed in treated male mice at 2000 mg/kg bw. Therefore, LD50 was considered to be > 2000 mg/kg bw when DDY male mice were treated with isopropyl 4-hydroxybenzoate orally.

In another prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for isopropyl 4-hydroxybenzoate. The LD50 was estimated to be 5799 mg/kg bw for rats.

Also it is further supported by experimental studies summarized by Andersen et al (International Journal of Toxicology, 2008, vol. 27, pp. 1-82, SUP4,) on structurally similar read across substance Butylparaben (CAS no 94-26-8), rat were treated with Butylparaben in the concentration of 5000 and 25000 mg/kg bw as 0.2 % or 0.3 % orally. No deaths were observed in treated rat at 5000 and 25000 mg/kg bw. Therefore, LD50 was considered to be > 5000 and 25000 mg/kg bw when rat were treated with Butylparaben orally.   

Thus, based on the above studies and predictions on isopropyl 4-hydroxybenzoate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, isopropyl 4-hydroxybenzoate can be “Not classified” as acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on isopropyl 4-hydroxybenzoate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, isopropyl 4-hydroxybenzoate can be “Not classified” as acute oral toxicity.