4,6-Dichloro-5-fluoropyrimidine

Endpoint summary

Description of key information

study according to OECD test guideline 404; result: corrosive

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

Study period:

2001-08-28 to 2001-10-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology KG D-24601 Lohndorf/Post Wankendorf
- Age at study initiation: approx 6-11 months
- Weight at study initiation: 2.3-2.9 kg

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Remarks:

dermal application to the shaved intact dorsal skin

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL/patch

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approx 6 cm²
- Type of wrap if used: The test substance was applied to the test site and then covered with a gauze patch. The patch was held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 60 min, 24, 48, 72 h and 4 to 14 days

SCORING SYSTEM: according to test guideline

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days, area of application dark discoloured, swelling on left abdomen increasing to: induration of the skin and skin in area of application discoloured and indurated, skin around area of application red and warm

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days, area of application dark discoloured, swelling on left abdomen increasing to: induration of the skin and skin in area of application discoloured and indurated, skin around area of application red and warm

Irritation parameter:

edema score

Basis:

animal: #1 - #3

Time point:

other: 60 min

Score:

2

Max. score:

4

Reversibility:

other: animals 1 and 3 died therafter

Irritation parameter:

erythema score

Basis:

animal: #1 - #3

Time point:

other: 60 min

Score:

1

Max. score:

4

Reversibility:

other: Animal 1 and 3 died thereafter

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

Under the present test conditions all three animals showed an erythema (grade 1) 1 hour after patch removal.
All three animals showed an oedema (grade 2) 1 hour after patch removal, animal no. 2 (grade 1) in addition at the examination time-points 24 and 48 hours after patch removal.
Additionally, dark discolouration of skin of the area of application and a swelling on the left abdomen were noted in animal no. two 24 hours to 14 days after patch removal. Induration of skin was noted in animal no. two 72 hours to 7 days after patch removal. Furthermore, from 8 to 14 days after patch removal discolouration and induration of the area of application was noted while the skin around this area was red and warm.
Animal nos. 1 and 3 were found dead at the examination time point 24 hours after patch removal.

Executive summary:

In a primary dermal irritation study according to OECD guideline 404 (1992), young adult Himalayan rabbits (3/treatment) were dermally exposed to 0.5 mL/patch of 4,6-dichlor-5-fluorpyrimidine (100 % a.i.) for 4 hours to 6 cm² of shaved dorsal skin. Animals then were observed for 14 days. Irritation was scored as required by the test guideline.

Under the present test conditions all three animals showed an erythema (grade 1) 1 hour after patch removal.

All three animals showed an oedema (grade 2) 1 hour after patch removal, animal no. 2 (grade 1) in addition at the examination time-points 24 and 48 hours after patch removal.

Additionally, dark discolouration of skin of the area of application and a swelling on the left abdomen were noted in animal no. two 24 hours to 14 days after patch removal. Induration of skin was noted in animal no. two 72 hours to 7 days after patch removal. Furthermore, from 8 to 14 days after patch removal discolouration and induration of the area of application was noted while the skin around this area was red and warm.

Animal nos. 1 and 3 were found dead at the examination time point 24 hours after patch removal. In this study, 4,6-dichlor-5-fluorpyrimidine is extremely irritating to the skin based on the presented results. Based on these results the test item is classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) as corrosive Category 1 (Causes severe skin burns and eye damage).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

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 does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin corrosion:

In a primary dermal irritation study according to OECD guideline 404 (1992), young adult Himalayan rabbits (3/treatment) were dermally exposed to 0.5 mL/patch of 4,6-dichlor-5-fluorpyrimidine (100 % a.i.) for 4 hours to 6 cm² of shaved dorsal skin. Animals then were observed for 14 days. Irritation was scored as required by the test guideline.

Under the present test conditions all three animals showed an erythema (grade 1) 1 hour after patch removal.

All three animals showed an oedema (grade 2) 1 hour after patch removal, animal no. 2 (grade 1) in addition at the examination time-points 24 and 48 hours after patch removal.

Additionally, dark discolouration of skin of the area of application and a swelling on the left abdomen were noted in animal no. two 24 hours to 14 days after patch removal. Induration of skin was noted in animal no. two 72 hours to 7 days after patch removal. Furthermore, from 8 to 14 days after patch removal discolouration and induration of the area of application was noted while the skin around this area was red and warm.

Animal nos. 1 and 3 were found dead at the examination time point 24 hours after patch removal. In this study, 4,6-dichlor-5-fluorpyrimidine is extremely irritating to the skin based on the presented results. Based on these results the test item is classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) as corrosive Category 1C (Causes severe skin burns and eye damage).

Justification for classification or non-classification

Based on the presented data 4,6-Dichloro-5-fluorpyrimidine needs to be classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally HArmonized System for Classification and Labelling of Chemicals (GHS) with regard to skin corrosion as 'Causes severe skin burns and eye damage' Category 1.

Based on this outcome the study for eye irritation was omitted and the substance was classified as 'Causes serious eye damage' Category 1 according to Regulation (EU) No. 1272/2008 (CLP) for precautionary reasons.