2,6-di-tert-butyl-α-dimethylamino-p-cresol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The analogue CAS No. 103-83-3 (benzyldimethylamine) which shares the same functional group with the substance CAS no. 88-27-7 (2,6-di-tert-butyl-α-dimethylamino-p-cresol), also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 103-83-3 can be used for the read-across approach.

Data source

Reference

Reference Type:

other: read-across

Title:

Unnamed

Year:

2012

Materials and methods

Principles of method if other than guideline:

Read-across approach from published data.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzyldimethylamine

EC Number:

203-149-1

EC Name:

Benzyldimethylamine

Cas Number:

103-83-3

IUPAC Name:

N,N-dimethyl-1-phenylmethanamine

Details on test material:

- Molecular formula (if other than submission substance): C9H13ON
- Molecular weight (if other than submission substance): 135.2
- Smiles notation (if other than submission substance): c1(ccccc1)CN(C)C
- InChl (if other than submission substance): InChI=1S/C9H13N/c1-10(2)8-9-6-4-3-5-7-9/h3-7H,8H2,1-2H3
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Any other information on results incl. tables

The analogue CAS No. 103-83-3 (benzyldimethylamine) which shares the same functional group with the substance CAS no. 88-27-7 (2,6-di-tert-butyl-α-dimethylamino-p-cresol), also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 103-83-3 can be used for the read-across approach.

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” (see attachment).

 

Table 1: Data Matrix, Analogue Approach

CAS Number		103-83-3	88-27-7
CHEMICAL NAME		Analogue N,N-dimethyl-1-phenylmethanamine	Target chemical 2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: < -10 °C	Experimental results: Handbook: 94 ºC
Boiling Point		Experimental results: 181 ºC	Weight of evidence: Handbook: 179 ºC (40 mm Hg) Estimated data: Boiling point EPISUITE = 336.78 ºC (Adapted Stein & Brown method) (MPBPWIN v1.43)
Density		No data	Experimental results: 1.023 at 20 ºC
Vapour Pressure		Estimated data: 0.587 mm Hg (25 ºC)	Estimated data: Vapour pressure EPISUITE = 1.69E-005 mm Hg at 25 ºC (Modified Grain method) (MPBPWIN v1.43) 0.00226 Pa at 25 ºC (Modified Grain method) (MPBPWIN v1.43)
Partition Coefficient (log Kow)		Experimental results: 1.98	Estimated data: The calculated partition coefficient is 4.24 (EPI Suite, KOWWIN v1.68 estimate).
Water solubility		Experimental results: 1.2E+004 mg/L (25 ºC)	Experimental results: 10.7 mg/L at 20 ºC (pH 9.2)
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Experimental results: No readily biodegradable	Estimated data: No readily biodegradable (BIOWIN v4.10)
Anaerobic Biodegradation		No data	No data
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Experimental results: 96-h LC50 = 37.8 mg/L   Estimated data: 96-h LC50 for fish is 33.75 mg/l (ECOSAR v1.00a, aliphatic amines class).	Key study: Estimated data: 96-h LC50 for fish is 1.346 mg/l (ECOSAR v1.00a, phenol amines class). 96-h LC50 for fish is 2.092 mg/l (ECOSAR v1.00a, aliphatic amines class). 96-h LC50 for fish is 0.907 mg/l (ECOSAR v1.00a, phenols class).
Acute Toxicity to Aquatic Invertebrates		Estimated data: 48-h LC50 for Daphnia is 3.23 mg/l (ECOSAR v1.00a, aliphatic amines class).	Key study: Estimated data: 48-h LC50 for Daphnia is 0.659 mg/l (ECOSAR v1.00a, phenol amines class) 48-h LC50 for Daphnia is 0.335 mg/l (ECOSAR v1.00a, aliphatic amines class) 48-h LC50 for Daphnia is 0.746 mg/l (ECOSAR v1.00a, phenols class)
Toxicity to Aquatic Plants		Estimated data: 96-h EC50 for algae is 1.277 mg/l (ECOSAR v1.00a, aliphatic amines class).	Key study: Estimated data: 96-h EC50 for green algae is 0.644 mg/l ECOSAR v1.00a, phenol amines class). 96-h EC50 for green algae is 0.297 mg/l (ECOSAR v1.00a, aliphatic amines class). 96-h EC50 for green algae is 2.760 mg/l (ECOSAR v1.00a, phenols class).
MAMMALIAN TOXICITY
Acute Oral		Experimental results: LD50 = 579 mg/kg	Experimental results: LD50 = 461 mg/kg
Acute Inhalation		Experimental results: LC50 = 2052 mg/m^3/4 h (liquid, vapours)	No data
Acute Dermal		Experimental results: LD50 =1477 mg/kg	Experimental results: LD50 > 4000 mg/kg
Skin irritation / Eye irritation		Experimental results: Corrosive	Experimental results: Not a skin irritant. Eye irritant.
Skin sensitisation		Experimental results: Not a skin sensitiser.	Experimental results: Skin sensitiser.
Repeated Dose		Repeated dose toxicity: oral: Key study: 28-day study in rats: NOAEL 50 mg/kg bw/day (both sexes)	Read-across: 28-day study in rats:   NOAEL 97 mg/kg bw/day (both sexes)
Genetic Toxicity in vitro	Gene mutation in bacteria	Key study: Negative	Read-across: Negative
	Chromosomal aberration	Key study:  Negative without metabolic activation. Positive with metabolic activation.	Read-across: Negative without metabolic activation. Positive with metabolic activation.
	Mammalian gene mutation	No data	No data
Genetic Toxicity in vivo		Key study: In vivo micronucleus study: Negative	Read-across: Negative
Carcinogenicity		No data	No data
Reproductive Toxicity: developmental toxicity		No data	No data

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Based on experimental data, the read-across approach is applied and the substance is considered as negative for the bacterial reverse mutation assay.

Executive summary:

The analogue CAS No. 103-83-3 (benzyldimethylamine) which shares the same functional group with the substance CAS no. 88-27-7 (2,6-di-tert-butyl-α-dimethylamino-p-cresol), also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 103-83-3 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the substance is considered as negative for the bacterial reverse mutation assay.