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Administrative data

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.
Reference:
Composition 0
Principles of method if other than guideline:
Read-across approach from data on an analogue.
GLP compliance:
no
Test material information:
Composition 1
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

Mode of Action Analysis / Human Relevance Framework

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.