Reaction mass of N,N-dimethyldecan-1-amide and N,N-dimethyloctanamide

Endpoint summary

Description of key information

Skin:

in vivo, rabbit, semiocclusive, 4h, OECD 404: Slight to severe skin reactions, erythema 3.3 and edema 3.0. Full reversibility was observed after 21 days (Clariant 1993, Kreiling)

Eye:

in vivo, rabbit, OECD 405, WoE: Slight to severe eye reactions, cornea opacity 1, iritis 1, conjunctivia redness 3 and chemosis 3, not reversible within 7 days (Clariant 1993, Kreiling).

in vivo, rabbit, OECD 405, WoE: Slight to severe eye reactions, cornea score 1.7, iris score 1, conjunctivia 2.7 and chemosis 4, not reversible within 4 days (Stepan 1990, Kreuzmann)

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted and documented study. In accordance with GLP and current guidelines.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF-Zucht, Chemisch pharmazeutische Fabrik Dr. Karl Thomae GmbH / 88400 Biberach / Germany
- Age at study initiation: 3-5 month
- Weight at study initiation: 3.0-3.2kg
- Housing: single cages in air-conditioned rooms
- Diet (e.g. ad libitum): Altromin 2123, ad libitum
- Water (e.g. ad libitum): deionized, chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 20 %
- Photoperiod (hrs dark / hrs light): 12h each

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml undiluted substance

Duration of treatment / exposure:

4h

Observation period:

0.5h, 24h, 48h and 72h as well as 7d, 14d and 21d after exposure

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5*2.5 cm
- Type of wrap if used: bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after exposure the test substance is removed using handwarm tap water
- Time after start of exposure:4h

SCORING SYSTEM:Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: average of 24h, 48h and 72h reading

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 21d

Irritation parameter:

edema score

Basis:

mean

Time point:

other: average of 24h, 48h and 72h reading

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21d

Irritant / corrosive response data:

0.5-1h after removing the patch all animal showed moderate to severe erythema and slight to severe edema. Average reading values (24h, 48h and 72h reading, mean from all animals) are:
erythema 3.3 and edema 3.0. Full reversibility was observed after 21 days, whereas a moderate erythema was could be observed at day 7 reading and slight erythema and edema were observed 14 day after exposure.
No signs of corrosion were reported.

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: other: EU GHS

Conclusions:

irritant

Executive summary:

To assess the irritant potential of Hoe S 4166 a skin irritation test according to EG-Guideline B.4. Akute Toxizität Hautreizung der Richtlinie 84/449/EWG fullfilling also the OECD guideline 404 was conducted. Therefore 3 New Zealand White rabbits were exposed to the test substance for 4h. After washing gradings were scored after 0.5h, 24h, 48h, 72h, 7d, 14d and 21d.

0.5-1h after removing the patch all animal showed moderate to severe erythema and slight to severe edema. Average reading values (24h, 48h and 72h reading, mean from all animals) are:

erythema 3.3 and edema 3.0. Full reversibility was observed after 21 days, whereas a moderate erythema was could be observed at day 7 reading and slight erythema and edema were observed 14 day after exposure.

No signs of corrosion were reported.

Based on this result the substance has to be labelled as irritating to skin according to EU GHS EC 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Valid experimental data is available for the assessment of skin and eye irritation for the registered substance.

Skin:

Studies according to OECD guidelines:

To assess the irritant potential of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamidea skin irritation test (Clariant 1993, Kreiling) according to EG-Guideline B.4. “Akute Toxizität Hautreizung der Richtlinie 84/449/EWG” fullfilling also the OECD guideline 404 was conducted. Therefore 3 New Zealand White rabbits were exposed to the test substance for 4h. After washing gradings were scored after 0.5h, 24h, 48h, 72h, 7d, 14d and 21d.

0.5-1h after removing the patch all animal showed moderate to severe erythema and slight to severe edema. Average reading values (24h, 48h and 72h reading, mean from all animals) are:

erythema 3.3 and edema 3.0. Full reversibility was observed after 21 days, whereas a moderate erythema could be observed at day 7 reading and slight erythema and edema were observed 14 day after exposure. No signs of corrosion were reported.

Based on this result the substance has to be labelled as irritating to skin according to EU GHS EC 1272/2008.

Studies according to other guidelines:

In a corrosivity study (Stepan 1990, S.R. Harris) the corrosive potential of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) was evaluated in general compliance with the conditions specified by the Department of Transportation Hazardous Materials Regulation (49 CFR). Therefore 6 New Zealand White rabbits were dermal exposed to 0.5ml test substance semi occlusive covered. Grading were recorded immediately, 24h and 48h after exposure.

Critical changes were noted in the coloration and/or texture of the skin included coriaceousness, light brown discoloration, and dark brown discoloration. No evidence of corrosion (necrosis) was found. Based on this information the test material is not c1assified as a corrosive by dermal application, as defined by the Department of Transportation Hazardous Material Regulation (49 CFR). No long term observation was performed. According to the registrant less information does not allow a classification according to GHS.

In another primary skin irritancy study (Stepan 1990, Kreuzmann) a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), the Toxic Substances Control Act (40 CFR), and the OECD Guidelines with the exception of the number of animals employed for testing. Therefore one New Zealand White rabbit was exposed to 0.5ml test substance for 4h semi occlusive covered. The application sites was scored for each rabbit approximately 1/2 - 1 hour, 24 hours, 48 hours, and 72 hours after application. Due to the suspected irritation potential of this test material, a single animal was initiated on this primary skin irritation study. Due to the effects exhibited in this single animal, this study was ultimately terminated without testing in additional animals. Severe irritation persisted 72 hours following application. The Primary Irritation Index (PII) was found to be 7.0 based on erythema and edema in the single animal tested. Critical changes noted in the coloration and/or texture of the skin included necrosis, slight fissures, coriaecousness, and light and dark brown discoloration. Evidence of corrosion (necrosis) was found. Although the full complement of animals was not used on this test, based on the findings in this single animal , the test material is classified in Toxicity Category I (40 CFR 156, Proposed by dermal administration).

Assessment of skin irritation / Assignment of key study.

Only one study (Clariant 1993, Kreiling) does fully comply with current guidelines including the prolonged observation time to assess irreversible effects. Two studies were conducted with main focus on CFR regulation limited by observation time and/or number of animals. Whereas one CFR compatible study (Stepan 1990, Kreuzmann) shows signs of corrosion a later performed study (Stepan 1990, S.R. Harris) assessing the corrosive potential could not confirmed the corrosive result. In result, due to the registrant, the substance has to be classified as severely irritating to skin. As long term observations are not performed in both CFR studies the reliability of both studies was degraded by the registrant.

In conclusion one study with a higher reliability, fully conducted to current guidelines is available (Clariant 1993, Kreiling). The registrant rates the results of this study as highest relevance confirmed by the results from one CFR compatible study. The corrosive result seen in one animal could not be explained and seem to be artifical. 

Due to the highest reliability the Clariant study (Clariant 1993, Kreiling) is assigned as key study.

 

Eye:

Studies according to OECD guidelines:

To assess the irritant potential of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide a eye irritation test according to EG-Guideline B.5. Akute Toxizität Augenreizung der Richtlinie 84/449/EWG fulfilling also the OECD guideline 405 was conducted (Clariant 1993, Kreiling). Therefore one New Zealand White rabbit was exposed to 0.1ml test substance and gradings were scored after 1h, 24h, 48h, 72h and 7 days. 1 h to 7 days after installation of the test substance a strong to crimson red conjunctivia as well as a clear swelling (up to half closed lid) was observed. Additional a clear iritis and diffuse to significant opacity was recorded. Clear discharge was seen during the whole experiment. The calculated scores (average of 24h, 48h and 72h) are: cornea opacity 1, iritis 1, conjunctivia redness 3 and chemosis 3. Effects observed were not reversible within the experiment (7d observation). After 7 days an increased vascularisation was noted.

Studies according to other guidelines

In another study (Stepan 1990, Kreuzmann) the primary ocular irritancy of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), the Toxic Substances Control Act (40 CFR), and the OECD Guidelines with the exception of the number of animals employed for testing. One New Zealand White rabbit was exposed to 0.1ml test substance and gradings were scored after 1h, 24h, 48h, 72h and 4 days. Due to the suspected irritation potential of this test material, a single animal was initiated on this primary eye irritation study. Due to the effects exhibited in this single animal, this study was ultimately terminated without testing in additional animals.

The test material produced corneal opacity, iritis, and conjunctival irritation persisting for the 4 day duration of this test when applied without rinsing to the eye of one New Zealand White rabbit. In addition, corneal vascularisation became apparent at day 4.

Irritation scores in the one animal are: cornea score 1.7, iris score 1, conjunctivia 2.7 and chemosis 4. No evidence of corrosion was noted in the animal.

 

Assessment of eye irritation / Assignment of key study.

Two studies of same quality are available assessing the eye irritation potential of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide. As both studies lead to the same results but were only conducted with one animal each, both were integrated into the dossier as WoE. Based on the gradings in both studies the substance has to be classified as “Irritating to eyes (Cat. 2)”. As hints were observed that irreversible effects might have been present (vascularisation) the classification “Irreversible effects on eye (Cat.1)" is assigned. Nevertheless it should be noted that both studies did not comply with the required observation period for irreversible effect.

In result an eye irritation potential without evidence of corrosion is concluded by the registrant and observations of a vascularisation in both experiment are rated as sign of irreversible effects.

Justification for selection of skin irritation / corrosion endpoint:

see Discussion

Justification for selection of eye irritation endpoint:

Weight of evidence: see discussion

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Classification skin irritation

Clear skin irritating effects were observed in a skin irritation study (Clariant 1993, Kreiling). The scores obtained from the study led to a classification as an irritating to skin (cat. 2) due to criteria of GHS (Regulation (EU) 1272/2008) and to classification irritating to skin R-38 according to EU-criteria DSD (67/548/EEC)

Labelling for skin irritation:

GHS: Irritating to skin (cat. 2)

DSD: Irritating to skin R-38

 

Classification eye irritation

Based on irreversible effects (vascularisation observed on day 4 or 7 after exposure) and the grading recorded for conjunctivia redness and chemosis the substance has to be labelled as irreversible effects on the eye (cat 1) due to criteria of GHS (Regulation (EU) 1272/2008) and Risk of serious eye damage R-41 according to EU-criteria DSD (67/548/EEC)

Labelling for eye irritation:

GHS: Irreversible effects on the eye (cat. 1)

DSD: Risk of serious eye damage R-41

Classification for respiratory irritation:
Based on irritating effects observed in a acute inhalation study (Bayer 1991, J. Pauluhn) the substance has to be labelled as STOT single cat 3 "May cause respiratory irritation" due to criteria of GHS (Regulation (EU) 1272/2008) and Irritating to respiratory system R 37 according to EU-criteria DSD (67/548/EEC