Methyl 2,5-dihydroxybenzoate

Endpoint summary

Description of key information

The substance was highly cytotoxic in the EpiOcular in-vitro assay (OECD 492, GLP) indicating a potention for irritation or irreversible damage to eyes. As the substance is a substituted resorcinol, the in-vivo data on resorcinol was taken into account for the decision to classify the substance as highly irritating to eyes (GHS Category 1)

 

Considering that resorcinol is not irritating to skin, it is not expected that methyl gentisate meets the criteria for GHS Classification as a skin irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: US FHSA, US Federal Register of Aug 12, 1961, pp 7333-7341, Part 191

Principles of method if other than guideline:

24h exposure to 0.5g moistend with water, scoring at 24h and 72h, on intact and abraded rabbit skin

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No details provided
Male albino rabbits

Type of coverage:

not specified

Preparation of test site:

other: intact and abraded

Vehicle:

physiological saline

Controls:

not specified

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

24h

Observation period:

14 days.

Number of animals:

6

Details on study design:

treated are were the bellies
Skin was either intact or abraded.
Scoring was done after 24h and after 72h

Irritation parameter:

edema score

Time point:

72 h

Score:

1.5

Max. score:

4

Remarks on result:

other: value for intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: value for intact skin

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

1.2

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: value for intact skin

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: value for intact skin

Irritant / corrosive response data:

Based on the PII, the substance is described by the authors as "not a primary irritant".

Other effects:

For sites of intact skin, treatment resulted in no perceptible to moderate findings.
If abraded skin was treated, the sites showed results ranging from not perceptible to necrosis. At the end of the 14-day period, the necrotic sites were either still incrusted or scarred. The other sites had healed and areas were free of signs of irritiation.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

Version / remarks:

09 Oct 2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF SE Experimental Toxicology and Ecology 67056 Ludwigshafen, Germany

Specific details on test material used for the study:

purity: 99.8%

Species:

human

Strain:

other: not applicable

Details on test animals or tissues and environmental conditions:

The EpiOcularTM model (OCL-200) is a three-dimensional non-keratinized tissue construct composed of normal human derived epidermal keratinozytes used to model the human corneal epithelium. The EpiOcularTM tissues (surface 0.6 cm²) are cultured on specially prepared cell culture inserts (MILLICELLs, 10 mm diameter) and are commercially available as kits (EpiOcular™ 200), containing 24 tissues on shipping agarose.

To assess the ability of the test material to directly reduce MTT a pretest was performed.

Vehicle:

unchanged (no vehicle)

Controls:

other: yes (tissue incubations for positive and negative controls included)

Amount / concentration applied:

bulk volume of ca. 50 μL

Duration of treatment / exposure:

6 hours

Duration of post- treatment incubation (in vitro):

18h

Number of animals or in vitro replicates:

Two tissue samples were used per group.

Details on study design:

Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the testsubstance treated epidermal tissues is compared to that of negative control tissues. The
quotient of the values indicates the relative tissue viability.

Irritation parameter:

other: viability

Remarks:

[%]

Run / experiment:

mean

Value:

ca. 6.7

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Methyl acetate was used as positive control and deionised water as negative control and both gave the results to satisfy acceptance criteria.

Methyl acetate decreased the mean viability to xx % of control cultures.

Interpretation of results:

other: GHS Cat 1 or 2

Conclusions:

The substance is at least irritating, if not highly irritating.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available