Dimethyl methylphosphonate

Endpoint summary

Description of key information

Skin Irritation: not irritating (Ciba 1976)

Eye Irritation: Serious eye damage CAT 1 (worst case assumption, Ciba 1976)

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:

other: scientifically acceptable study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Draize test

GLP compliance:

no

Remarks:

well documented study

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: rabbits (3 males; 3 females) of the Russian breed; no additional data
- Age at study initiation: no data
- Weight at study initiation: 1.7-2.0 kg
- Housing: housed singly in metal cages (overall dimensions 47x32x34 cm)
- Diet (e.g. ad libitum): standard diet of Nafag
- Water (e.g. ad libitum): drinking water
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±1°C
- Humidity (%): 55±5%
- Photoperiod (hrs dark / hrs light): 14 hours light/day

Type of coverage:

occlusive

Preparation of test site:

other: shaved (right side) and abraded (shaved skin area on the left side was slightly scarified just before treatment)

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100%

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Area of exposure: a gauze patch of 2.5 x 2.5 cm laden with the test substance was applied immediately to the prepared skin
- % coverage: not specified
- Type of wrap if used: the patch was covered with an impermeable foil of 5 x 5 cm, which was fixed to the body of the animals with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified; the gauze patches were removed
- Time after start of exposure: 24 hours after application

SCORING SYSTEM: comparable to the OECD scoring system; the reaction of the skin was appraised upon removal during an observation period of 7 days.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all tested animals

Time point:

other: 24-48-72-hour

Score:

0.28

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Only shaved sites considered for evaluation; 5 animals (3 males and 2 females) showed an erythema score of each 1, reversible within 48 hours (see Table 1)

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all tested animals

Time point:

other: 24-48-72-hour

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Only shaved sites considered for evaluation (see Table 2)

Irritant / corrosive response data:

see Table 1&2; a slight irritating effect was present on abraded sites (maximum score of 2 in only one animal after 24 hours), but fully reversible within 72 hours in all animals

Table 1: Erythema scores assuming (only shaved sites shown)

Time point	Individual and mean erythema scores
	Male animals			Male animals			Mean all animals
	1^st	2^nd	3^rd	4^th	5^th	6^th
24 h	1	1	1	1	0	1	0.83
48 h	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0
Mean 24-48-72 h	0.3	0.3	0.3	0.3	0	0.3	0.28

 

Table 2: Edema scores (only shaved sites shown)

Time point	Individual and mean edema scores
	Male animals			Male animals			Mean all animals
	1^st	2^nd	3^rd	4^th	5^th	6^th
24 h	0	0	0	0	0	0	0
48 h	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0
Mean 24-48-72 h	0	0	0	0	0	0	0

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Draize test

GLP compliance:

no

Remarks:

well documented study

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: rabbits (3 males; 3 females) of the Russian breed; no additional data
- Age at study initiation: no data
- Weight at study initiation: 1.6-2.0 kg
- Housing: housed singly in metal cages (overall dimensions 47x32x34 cm)
- Diet (e.g. ad libitum): standard diet of Nafag
- Water (e.g. ad libitum): drinking water
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±1°C
- Humidity (%): 55±5%
- Photoperiod (hrs dark / hrs light): 14 hours light/day
Only rabbits showing normal ophthalmic findings were included in the test.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml of the test substance were introduced into the conjunctival sac of the left eye with a syringe
- Concentration (if solution): 100%

Duration of treatment / exposure:

After application, the eyelids were held open for a few seconds

Observation period (in vivo):

up to 8 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
The eyes of 3 animals were rinsed 1 minute after application with physiologic saline

SCORING SYSTEM: comparable to the OECD scoring system
The reactions were appraised with a slit lamp after 1 and 6 hours, 1, 2, 3, 6 and 8 days; the results of washed eye animals are not considered hier because they are not comparable to the OECD guideline (evaluation of eye irritation).

Irritation parameter:

cornea opacity score

Remarks:

corneal opacity

Basis:

mean

Remarks:

of the 3 selected animals (no wash out)

Time point:

other: 24-48-72-hour

Score:

1.8

Max. score:

4

Reversibility:

not fully reversible within: 8 days (one animal still showed a score of 1)

Remarks on result:

other: individual mean was 2.0, 1.7 and 1.7 for the 3 animals considered

Irritation parameter:

iris score

Basis:

mean

Remarks:

of the 3 selected animals (no wash out)

Time point:

other: 24-48-72-hours

Score:

0.5

Max. score:

2

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Individual means were 1.0, 0.3 and 0.3

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

mean

Remarks:

of the 3 selected animals (no wash out)

Time point:

other: 24-48-72-hour

Score:

2.6

Max. score:

3

Reversibility:

not fully reversible within: 8 days (only one animal still present a score of 2)

Remarks on result:

other: Individual mean scores were 3.0, 2.0 and 2.9

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of the 3 selected animals (no wash out)

Time point:

other: 24-48-72-hour

Score:

1.9

Max. score:

4

Reversibility:

not fully reversible within: 8 days (only one animal still present a score of 1)

Remarks on result:

other: Individual mean scores were 2.3, 1.5 and 2.0

Irritant / corrosive response data:

based on the irritation scores (see above and Table 1) and on the conjunctival redness in particular, the test substance is irritating to the rabbit eyes

Table 1: Draize scores

time	Test animal	Cornea		Iris	Conjunctiva
		Opacity	Area		Erythema	Edema	Secretion
After 1 hours	First	2	4	1	2	3	2
	Second	2	4	1	2	2	2
	Third	1	4	1	2	3	2
After 24 hours	First	2	4	1	3	3	2
	Second	2	4	1	3	2	2
	Third	2	4	1	3	3	2
After 48 hours	First	2	4	1	3	2	2
	Second	2	4	0	2	1	1
	Third	2	4	0	3	2	2
After 72 hours	First	2	4	1	3	2	2
	Second	1	4	0	1	0	0
	Third	1	4	0	2	1	0
After 8 days	First	1	4	0	2	1	0
	Second	0	0	0	0	0	0
	Third	0	0	0	0	0	0
24-72-72-hour mean (2-animals mean is calculated for those 2 animals showing the worst reactions	First	2.0	4.0	1.0	3.0	2.3	2.0
	Second	1.7	4.0	0.3	2.0	1.5	1.5
	Third	1.7	4.0	0.3	2.7	2.0	1.3
	3-animals mean	1.8	4.0	0.5	2.6	1.9	1.6

Interpretation of results:

other: Results may lead to CAT 2A but reversibility investigation gap, hence worst case CAT 1 assumed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

Skin Irritation: For skin irritation the key study conducted according to the draize protocol does not show sufficient scorings for skin irritation labeling according to Regulation 1272/2008.

Eye Irritation: Concerning eye irritation the most reliable study shows gradings lead to eye irritation cat. 2 but the reversible was not fully investigated up to day 21. Instead readings on day 8 (last day of investigation) show still effects in one animal. It can be assumed that due less severe readings on day 8 the effects will fully disappear at a later stage, but as this was not investigated and stays unclear. Therefore reversible can not fully be show and according to Regulation 1272/2008 the substance needs to be classified as CAT 1 eye damaging.

As a result DMMP is not considered to be classified as a skin irritant under Regulation (EC) No. 1272/2008 but as eye damaging CAT 1.