Methyl 4-hydroxybenzoate

Endpoint summary

Description of key information

Oral:
- male rats, LD50: 2100 mg/kg bw
- male rats, LD50: > 5000 mg/kg bw
- male mice, LD50: > 5600 mg/kg bw
- mice, LD50: > 8000 mg/kg bw
- female rats, LD50: > 15,000 mg/kg bw
- guinea pigs, LD50: 3000 mg/kg bw
- male dogs, LD50: > 2000 mg/kg bw
- female rabbits, LD50: > 2000 mg/kg bw
- dogs: LD50: 3000 mg/kg bw

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

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study design similar to current OECD guideline, but no results for individual animals reported, short reporting.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Remarks:

study performed before OECD guidelines

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- male rats
- source: Flow Laboratories
- average body weight: 250 g
- age at study initiation: ten to twelve weeks

DIET
- A commercial 4% fat diest was fed to all animals.
- Water: ad libitum

HOUSING
Animlas were held in quarantine for 4-11 days.
Cages: Sanitary cages and bedding were used, and changed two times per week, at which time water containers were cleaned, sanitized and filled. Once a week, cages were repositioned on racks; racks were repositioned within rooms monthly. Personnel handling animals or working within animal facilities wore head coverings and face masks, as wel as suitable garments. Individuals with respiratory or other overt infections were excluded from the animal facilities.

Route of administration:

oral: gavage

Vehicle:

other: 0.85% saline

Details on oral exposure:

Compound FDA 71-38 was suspended in 0.85% saline and administered by intubation.

Doses:

100 mg/kg body weight
500 mg/kg body weight
1000 mg/kg body weight
2000 mg/kg body weight
3000 mg/kg body weight
4000 mg/kg body weight

No. of animals per sex per dose:

5 male rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: no data
- Necropsy performed: yes

Statistics:

Probit analysis, Litchfield-Wilcoxson method.

Preliminary study:

Compound FDA 71-38 was suspended in 0.85% saline and administered to ten male rats by intubation. The average weight of the animals was 250 g and each received a dose of 5000 mg/kg. All animals were found dead within 24 hours. Necropsy showed reddened stomach lining and congested lung.

Sex:

male

Dose descriptor:

LD50

Effect level:

2 100 mg/kg bw

95% CL:

> 1 320 - < 3 340

Mortality:

Dose: 100 mg/kg bw, Mortality rate: 0 / 5
Dose: 500 mg/kg bw, Mortality rate: 0 / 5
Dose: 1000 mg/kg bw, Mortality rate: 1 / 5
Dose: 2000 mg/kg bw, Mortality rate: 2 / 5
Dose: 3000 mg/kg bw, Mortality rate: 4 / 5
Dose: 4000 mg/kg bw, Mortality rate: 4 / 5

Clinical signs:

other: - no clinical signs reported

Gross pathology:

Necropsy revealed the following signs of toxicity:
reddened stomach lining, lung congested.

Other findings:

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of Methylparaben (LD50) was determined to be 2100 mg per kg body weight. Based on the result of this study Methylparaben is not subject for labelling and classification requirements according to regulatory requirements.

Executive summary:

The median lethal dose of Methylparaben (LD50) was determined to be 2100 mg per kg body weight. Based on the result of this study Methylparaben is not subject for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 100 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A number of reliable studies plus supporting information is available in multiple species for the acute oral toxicity of Methylparaben. A well documented study showed that male rats were more sensitive than mice. The lowest reliable LD₅₀determined was 2100 mg/kg bw for male Sprague Dawley rats. All results are shown in the “Short description of key information” field.

Justification for classification or non-classification

Due to the findings described above (LD50 oral in rats 2100 mg/kg bw) Methylparaben has not to be classified as acute orally toxic.

It can reasonably be deduced that Methylparaben does not exert systemic toxic effects after dermal application and thus does not have to be classified, because Methylparaben did not cause lethal effects after administration of a single oral dose of up to 2100 mg/kg bw in rats. Furthermore the substance does not have to be classified as skin irritating and it is unlikely that higher amounts than tested in the acute oral toxicity study will be systemically available via the intact skin barrier. Therefore, testing is not scientifically necessary.

In accordance with Section 1.2 of REACH Annex XI, there is sufficient weight of evidence from several independent sources of information leading to the conclusion that Methylparaben does not exert systemic toxic effects after acute inhalation exposure and thus does not have to be classified, because

- the LD50 value for acute oral toxicity of Methylparaben is >2000 mg/kg bw,

- Methylparaben does not have to be classified as skin irritating, and

- inhalation to consumer is very unlikely to occur, since the substance is embedded in cosmetical matrices for application by the consumer

- risk characterisation calculations show that there is no concern for workers arising from the Methylparaben production (for calculation details please refer to “Waiver_Acute toxicity: inhalation”).

Therefore, it is concluded that testing of acute inhalation toxicity of Methylparaben is not scientifically necessary.