Hexahydromethylphthalic anhydride

Endpoint summary

Description of key information

Skin:

MHHPA is, based on the available information (erythema score 2.00, oedema score 2.25), not a dermal irritant according to the Regulation (EC) No 1272/2008 (CLP). 

The conditions of the available study are more stringed, in particular the 24 hour exposure period compared with 4 hours of current test methods (described in OECD TG 404), and are thus regarded as worst case scenario. In conclusion the substance is not classified skin irritating based on CLP.

 

Eye:

Highly irritating and classified as Seriously eye damaging according to the Regulation (EC) No 1272/2008 (CLP) when 0.1 mL is applied to the rabbit eye.

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FHSA - 16CFR1500.41

Deviations:

no

Principles of method if other than guideline:

24 hour exposure period on abraded and intact skin. Treated sites examined for reaction to treatment 24 and 72 hours following exposure.

GLP compliance:

yes

Specific details on test material used for the study:

Lot/batch No.: 013

Species:

rabbit

Strain:

other: Albino

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Test sites: One abraded, one intact site / animal
- Type of wrap if used: Test substance placed onto surgical gauze patches held in contact with the skin by adhesive tape. Trunk of the animal then wrapped with impervious tape for duration of exposure period

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize scale
Scoring was done after 24 and 72 h.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

4.4

Max. score:

8

Reversibility:

not specified

Remarks on result:

other:

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

2.25

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Intact skin

Remarks:

FHSA test - Observation at 24 & 72 hours only

Intact skin
Animal No.	Erythema		Oedema
	24 hours	72 hours	24 hours	72 hours
1	2	2	2	2
2	2	2	2	3
3	2	2	2	2
4	1	3	1	3
5	2	2	2	3
6	2	2	2	3
Mean	2.0		2.3

 

Abraded skin
Animal No.	Erythema		Oedema
	24 hours	72 hours	24 hours	72 hours
1	2	2	3	2
2	2	2	2	3
3	2	2	2	2
4	1	3	1	3
5	2	4	2	3
6	2	2	2	3
Mean	2.2		2.3

Interpretation of results:

GHS criteria not met

Conclusions:

Primary skin irritation has been investigated according to FHSA test methods. Based on the available information, (erythema score 2.00, oedema score 2.25), the substance is not a dermal irritant according to CLP (Regulation (EC) No 1272/2008).
The conditions of the available study are more stringed, in particular the 24 hour exposure period compared with 4 hours of current test methods (described in OECD TG 404), and are thus regarded as worst case scenario. In conclusion the substance is not classified skin irritating based on CLP.

Executive summary:

In a primary dermal irritation study, rabbits were dermally exposed to 0.5 mL of MHHPA for 24 hours. Reaction was assessed after 24 and 72 hours and assigned a numerical score according to the Draize scale.

A mean erythema score (24 - 72 hours), calculated over all 6 animals, for intact skin of 2.00 and for abraded skin of 2.33 was observed. The oedema score was determined to be 2.25 for intact skin and 2.67 for abraded skin.

Taking the test conditions into account, in particular the 24 hour exposure period compared with 4 hours of current test methods described in OECD TG 404, MHHPA has not to be classified and labelled as dermal irritant according to CLP (Regulation (EC) No 1272/2008).

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

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because the substance is classified as irritating to eyes with risk of serious damage to eyes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin:

In a primary dermal irritation study, rabbits were dermally exposed to 0.5 mL of MHHPA for 24 hours. Reaction was assessed after 24 and 72 hours and assigned a numerical score according to the Draize scale. A mean erythema score (24 - 72 hours),calculated over all 6 animals, for intact skin of 2.00 and for abraded skin of 2.33 was observed. The oedema score was determined to be 2.25 for intact skin and 2.67 for abraded skin. Taking the test conditions into account, in particular the 24 hour exposure period compared with 4 hours of current test methods described in OECD TG 404, MHHPA has not to be classified and labelled as dermal irritant according to CLP.

Eye:

MHHPA is classified as seriously eye damaging and CLP cites the need for hazard statement H318 (causes serious eye damage). Testing is waived based on the existing classification.

Justification for classification or non-classification

Based on the available data MHHPA was classified and labelled as Cat. 1, H318 causes serious eye damage, according to the Regulation (EC) No 1272/2008 (CLP).