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

Endpoint summary

Description of key information

The study with the longest duration and lowest NOAEL was chosen as key study (read-across approach).
Klimisch 2. Read-across approach. 
The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) 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. 128 -37-0 can be used for the read-across approach. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral

Remarks:

other: read-across from several repeated dose toxicity studies, including chronic data

Type of information:

migrated 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: see 'Remark'

Remarks:

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) 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. 128 -37-0 can be used for the read-across approach.

Principles of method if other than guideline:

Read-across approach from data on an analogue.

GLP compliance:

no

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Critical effects observed:

not specified

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) 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. 128 -37-0 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		128-37-0	88-27-7
CHEMICAL NAME		Analogue 2,6-di-tert-butyl-4-methylphenol	Target chemical 2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 69.8 - 71 ºC	Experimental results: Handbook: 94 ºC
Boiling Point		Experimental results: 265 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		Experimental results: 1.048 at 20 ºC	Experimental results: 1.023 at 20 ºC
Vapour Pressure		Experimental results: 3.82 Pa at 24.85 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: Log Pow = 5.2	Estimated data: The calculated partition coefficient is 4.24 (EPI Suite, KOWWIN v1.68 estimate).
Water solubility		Experimental results: 0.4 -0.6 mg/l at 20-25 ºC	Experimental results: 10.7 mg/L at 20 ºC (pH 9.2)
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Estimated data: Not readily biodegradable	Estimated data: No readily biodegradable (BIOWIN v4.10)
Anaerobic Biodegradation		No data	No data
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Estimated data: ECOSAR LC50 (96 h) = 0.2 mg/l	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		Experimental results: EC50 (48 h) =mg/L	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: ECOSAR EC50 (96 h) = 0.76 mg/L	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 >6000 mg/kg bw (rats)	Experimental results: LD50 = 461 mg/kg
Acute Inhalation		No data	No data
Acute Dermal		Experimental results: LD50 >2000 mg/kg bw (rats)	Experimental results: LD50 > 4000 mg/kg
Skin irritation / Eye irritation		No data	Experimental results: Not a skin irritant. Eye irritant.
Skin sensitisation		Experimental results: Weight of evidence: Not a skin sensitizer.	Experimental results: Skin sensitiser.
Repeated Dose		Experimental results: Weight of evidence: NOAEL from chronic study: 25 mg/kg bw/day	Read-across: NOAEL from chronic study: 30 mg/kg bw/day
Genetic Toxicity in vitro	Gene mutation in bacteria	Experimental results: Negative	Read-across: Negative
	Chromosomal aberration	Experimental results: Weight of evidence: Negative	Read-across: Negative
	Mammalian gene mutation	Experimental results: Weight of evidence: Negative	Read-across: Negative
Genetic Toxicity in vivo		Experimental results: Weight of evidence: Negative	Read-across: Negative
Carcinogenicity		Experimental results: Weight of evidence: Not classified as carcinogenic.	No data
Reproductive Toxicity: developmental toxicity		Experimental results: Weight of evidence:   Effects on fertility: NOAEL: 25 mg/kg bw/day in the rat.   Developmental toxicity: No data	Read-across: Effects on fertility: NOAEL: 30 mg/kg bw/day in the rat.       Developmental toxicity: No data

Conclusions:

Based on experimental data, the read-across approach is applied and the NOAEL is considered to be 30 mg/kg bw/day.

Executive summary:

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) 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. 128 -37-0 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 30 mg/kg bw/day.

Endpoint conclusion

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Klimisch 2. Read-across approach.

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) 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. 128 -37-0 can be used for the read-across approach.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study with the longest duration and lowest NOAEL was chosen as key study (read-across approach).

Justification for classification or non-classification

Based on the available data, the substance is not classified for repeated dose toxicity.