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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
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 data on an analogue.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Effect levels

Dose descriptor:
NOAEL
Effect level:
97 other: mg/kg bw/day
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

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/m3/4 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:
Based on experimental data, the read-across approach is applied and the NOAEL is considered to be 97 mg/kg bw/day.
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 NOAEL is considered to be 97 mg/kg bw/day.