3-(dimethylamino)propylurea

Endpoint summary

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:

2000

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:

This study was designed to comply with the standards set forth in 49 CFR 173.137 which directs that this study be conducted according to the July 1992 OECD Guideline for Testing of Chemicals, Number 404, "Acute Dermal InitationlCorrosionn.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

The test article was kept in contact with the skin for three (3) minutes and scored for erythema and edema one hour following patch removal. Since the 3 minute exposure did not produce a definitive effect, two additional rabbits were added to the study. All three animals were dosed at site #2 for an exposure period of 1 hour and at site #3 for a four hour exposure. Each site was scored for erythema and edema one hour following patch removal, at 24, 48 and 72 hours and again on days 7 and 14.

Observation period:

Animals were observed for systemic signs at each dermal scoring interval.

Number of animals:

3 New Zealand White rabbits

Details on study design:

New Zealand White rabbits were received from Ace Animals, Boyertown, PA on 12/21/99. Following a quarantine period of at least one week, three healthy New Zealand White rabbits were selected for this test from a larger group.
The animals were born the weeks of 10/10 through 10/24/99. The pretest body weight was 2.0 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed llcage in suspended cages. Bedding was placed beneath the cages and changed at least three timeslweek. Fresh Purina Rabbit Chow (Diet #5321) was provided daily. Water was available libitum.
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour lightidark cycle and was kept clean and vermin free.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

3 minute exposure: There was no erythema or edema.
1 hour exposure: There was no erythema or edema.
4 hour exposure: There was no erythema or edema.

Other effects:

Two animals had diarrhea and soiling of the anogenital area. The remaining animal appeared normal during the observation period. Body weight changes were normal.

Interpretation of results:

GHS criteria not met

Conclusions:

NE 1060 is not corrosive to rabbit skin. The modified Primarv Irritation Index is 0.

Executive summary:

The purpose of this study was to determine if the test article causes irreversible damage when applied to the rabbit skin.

Initially, one healthy New Zealand White rabbit was placed in a restrainer and dosed with NE 1060. The test article (0.5 ml) was placed on the intact skin of the back (Site 1). The test article was kept in contact

with the skin for three (3) minutes and scored for erythema and edema one hour following patch removal. Since the 3 minute exposure did not produce a definitive effect, two additional rabbits were added to the

study. All three animals were dosed at Site 2 for an exposure period of 1 hour and at Site 3 for a four hour exposure. Each site was scored for erythema and edema one hour following patch removal, at 24, 48, and 72 hours and again on Days 7 and 14. Animals were observed for systemic signs at each dermal scoring interval. A modified primary irritation index was calculated. Body weights were recorded pretest and at termination.

3 minute exposure: There was no erythema or edema.

1 hour exposure: There was no erythema or edema.

4 hour exposure: There was no erythema or edema.

Systemic observations: Two animals had diarrhea and soiling of the anogenital area. The remaining animal appeared normal during the observation period. Body weight changes were normal.

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

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

This study was designed to comply with the standards set forth in OECD Guidelines For Testing Chemicals, Number 405, adopted February 24, 1987.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

New Zealand White rabbits were received from Ace Animals, Boyertown, PA on 12/21/99 and quarantined for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva.
A Mini-Maglite flashlight equipped with a high intensity bulb was used to aid in the examination. Three rabbits (males), free from evidence of ocular irritation or abnormalities, were assigned to this study.
The animals were born the weeks of 10/10 through 10/24/99. The pretest body weight was 2.1 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed llcage in suspended cages. Bedding was placed beneath the cages and changed at least three times week. Fresh Purina Rabbit Chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour lightldark cycle and was kept clean and vermin free.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

One eye of each rabbit was dosed. The contralateral eye sewed as a control. The test article (0.1 ml) was placed by syringe into the conjunctival sac which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article.

Duration of treatment / exposure:

Using a Mini-Maglite flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48, and 72 hours post dose and on day 7.
Ocular reactions were graded according to the numerical Draize technique. Additional signs were described.

Observation period (in vivo):

1, 24, 48, and 72 hours post dose and on day 7

Number of animals or in vitro replicates:

Three healthy New Zealand White rabbits (males)

Details on study design:

Three healthy New Zealand White rabbits (males), free from evidence of ocular initation and corneal abnormalities, were dosed with NE 1060. The test article (0.1 ml) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined and scored by the Draize technique at 1,24,48 and 72 hours post dose and on day 7. The primary eye irritation score for each rabbit, each day, was calculated. Body weights were recorded pretest

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 65 - <= 85

Max. score:

85

Reversibility:

not reversible

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

24/48/72 h

Score:

63

Max. score:

63

Reversibility:

not reversible

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 38 - <= 63

Max. score:

63

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 40 - <= 60

Max. score:

60

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

40

Max. score:

40

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 15 - <= 40

Max. score:

40

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 18 - <= 20

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

18

Max. score:

18

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

18

Max. score:

18

Reversibility:

not reversible

Irritant / corrosive response data:

Corneal opacity, iritis and conjunctival irritation persisted through day 7.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

NE 1060 is corrosive

Executive summary:

Corneal opacity, intis and conjunctival irritation persisted through day 7. One instance of soiling of the anogenital area was noted during the observation period.

Conclusion: NE 1060 is corrosive.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)