N,N-diethyl-3-oxobutyramide

Endpoint summary

Description of key information

Skin Sensitization:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation, other

Remarks:

skin sensitization: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Weight of evidence approach based on structurally similar chemicals

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: weight of evidence based on structurally similar chemicals

Principles of method if other than guideline:

The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal sensitization potential of N,N-diethyl-3-oxobutanamide

GLP compliance:

not specified

Type of study:

other: Weight of evidence approach based on similar chemicals

Specific details on test material used for the study:

- Name of test material: N,N-diethyl-3-oxobutanamide- Molecular formula: C8H15NO2- Molecular weight: 157.212 g/mol- Smiles notation: N(C(CC(C)=O)=O)(CC)CC- InChl : 1S/C8H15NO2/c1-4-9(5-2)8(11)6-7(3)10/h4-6H2,1-3H3- Substance type: Organic- Physical state: Liquid

Species:

other: guinea pigs and mice

Strain:

not specified

Sex:

female

Route:

intradermal and epicutaneous

Vehicle:

olive oil

Concentration / amount:

intradermal injection of 10,000 ppm in olive oil andtopical treatment with a 50,000 ppm solution in olive oil.

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, open

Vehicle:

physiological saline

Concentration / amount:

intradermal injection of 10,000 ppm in olive oil andtopical treatment with a 50,000 ppm solution in olive oil.

Adequacy of challenge:

other: various not irritating concentrations of the test chemical were used for challenge

No. of animals per dose:

10 guineapigs/dose

Details on study design:

The study is based on weight of evidence approach from the read across values

Challenge controls:

The study is based on weight of evidence approach from the read across values

Positive control substance(s):

not specified

Vehicle:

other: acetone

Concentration:

25 microliters

No. of animals per dose:

no data available

Details on study design:

The study is based on weight of evidence approach from the read across values

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no response observed

Remarks on result:

no indication of skin sensitisation

Parameter:

SI

Value:

> 3

Test group / Remarks:

test group

Remarks on result:

other: not sensitizing

Interpretation of results:

other: not sensitizing

Conclusions:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not sensitizing to skin.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of N,N-diethyl-3 -oxobutanamide.

The dermal sensitization potential ofthe structurally similar test chemical was evaluated in a mouse local lymphnode assay(LLNA). The study was performed as per OECD 429 Guidelines. Groups of female CBA mice (7-12 weeks of age) were exposed topically on the dorsum of both ears to 25µl of the test material or to an equal volume of relevant vehicle only. Treatment was performed daily for 3 consecutive days.Five days after the initiation of exposure, all mice were injected via the tail vein with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine. Mice were sacrificed 5 hours later, and the draining auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by beta scintillation counting was reported in disintegrations per minute (dpm). A stimulation index (SI) was calculated for each chemical-treated group as the ratio of the dpm of the treated group (or mean dpm when individual animals were assessed) to the dpm or mean dpm of the concurrent vehicle control group.The approach to estimation of the relative skin sensitization potential was based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value.A substance was classified as a skin sensitizer if it induced a threefold or greater increase in local lymph node proliferative activity at one or more test concentrations when compared with concurrent vehicle-treated controls (SI≥3).The relative potency index of the test chemical couldnot be calculated as its mean SI value was below 3(SI = 1.3).

Based on the relative potency index, the test chemical was considered to be a non sensitizer.

This is supported by the results of a guinea pig maximization test conducted to evaluate the dermal sensitization potential of the other structurally similar chemical. The test was performed according to Magnusson and Kligman method. Female Hartley guinea pigs were used for the study. 10 guinea pigs/doses were used for the induction, challenge exposure and 10 guinea pigs were used as controls. Induction was made via intradermal injection of 10,000 ppm in olive oil and topical treatment with a 50,000 ppm solution in olive oil.

After a rest of 21 days, the guinea pigs were challenged with various non-irritating doses of the test chemical.

0.1ml of 0, 1,250, 2,500, 5,000 and 10,000 ppm in saline was applied topically to guinea pig skin and observed for signs of dermal reactions after 48 hours of challenge exposure.

No signs of sensitization were observed in any of the test or control guinea pigs challenged with the test chemical.Hence the test chemical was considered to be not sensitizing to guinea pig skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not sensitizing to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of N,N-diethyl-3 -oxobutanamide.

The dermal sensitization potential ofthe structurally similar test chemical was evaluated in a mouse local lymphnode assay(LLNA). The study was performed as per OECD 429 Guidelines. Groups of female CBA mice (7-12 weeks of age) were exposed topically on the dorsum of both ears to 25µl of the test material or to an equal volume of relevant vehicle only. Treatment was performed daily for 3 consecutive days.Five days after the initiation of exposure, all mice were injected via the tail vein with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine. Mice were sacrificed 5 hours later, and the draining auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by beta scintillation counting was reported in disintegrations per minute (dpm). A stimulation index (SI) was calculated for each chemical-treated group as the ratio of the dpm of the treated group (or mean dpm when individual animals were assessed) to the dpm or mean dpm of the concurrent vehicle control group.The approach to estimation of the relative skin sensitization potential was based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value.A substance was classified as a skin sensitizer if it induced a threefold or greater increase in local lymph node proliferative activity at one or more test concentrations when compared with concurrent vehicle-treated controls (SI≥3).The relative potency index of the test chemical couldnot be calculated as its mean SI value was below 3(SI = 1.3).

Based on the relative potency index, the test chemical was considered to be a non sensitizer.

This is supported by the results of a guinea pig maximization test conducted to evaluate the dermal sensitization potential of the other structurally similar chemical. The test was performed according to Magnusson and Kligman method. Female Hartley guinea pigs were used for the study. 10 guinea pigs/doses were used for the induction, challenge exposure and 10 guinea pigs were used as controls. Induction was made via intradermal injection of 10,000 ppm in olive oil and topical treatment with a 50,000 ppm solution in olive oil.

After a rest of 21 days, the guinea pigs were challenged with various non-irritating doses of the test chemical.

0.1ml of 0, 1,250, 2,500, 5,000 and 10,000 ppm in saline was applied topically to guinea pig skin and observed for signs of dermal reactions after 48 hours of challenge exposure.

No signs of sensitization were observed in any of the test or control guinea pigs challenged with the test chemical.Hence the test chemical was considered to be not sensitizing to guinea pig skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that N,N-diethyl-3-oxobutanamide can be not sensitizing to skin.

Hence by applying the weight of evidence approach, N,N-diethyl-3-oxobutanamide can be considered to be not sensitizing to skin. It can be classified under the category “Not Classified” as per CLP regulation.