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

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

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. 119-47-1 (6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol) which shares the same functional group (alkylphenol) with the substance CAS no. 88-27-7 (2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 119-47-1 can be used for the read-across approach.

Data source

Reference

Reference Type:

other: read-across

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

Principles of method if other than guideline:

Read-across from published data on an analogue.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol

EC Number:

204-327-1

EC Name:

6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol

Cas Number:

119-47-1

IUPAC Name:

2,2'-methylenebis(6-tert-butyl-4-methylphenol)

Details on test material:

- Molecular formula (if other than submission substance): C23H32O2
- Molecular weight (if other than submission substance): 340.5
- Smiles notation (if other than submission substance): c1(c(c(cc(c1)C)C(C)(C)C)O)Cc1c(c(cc(c1)C)C(C)(C)C)O
- InChl (if other than submission substance): InChI=1/C23H32O2/c1-14-9-16(20(24)18(11-14)22(3,4)5)13-17-10-15(2)12-19(21(17)25)23(6,7)8/h9-12,24-25H,13H2,1-8H3
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

72 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

290 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

The analogue CAS No. 119-47-1 (6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol) which shares the same functional group (alkylphenol) with the substance CAS no. 88-27-7 (2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 119-47-1 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		119-47-1	88-27-7
CHEMICAL NAME		Analogue 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol	Target chemical 2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 118-128 ºC	Experimental results: Handbook: 94 ºC
Boiling Point		No data	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: 3.3E-07 Pa at 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: Log Pow = 6.25	Estimated data: The calculated partition coefficient is 4.24 (EPI Suite, KOWWIN v1.68 estimate).
Water solubility		Experimental results: 0.02mg/l at 25 ºC	Experimental results: 10.7 mg/L at 20 ºC (pH 9.2)
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Estimated and experimental data: Not readily biodegradable	Estimated data: No readily biodegradable (BIOWIN v4.10)
Anaerobic Biodegradation		No data	No data
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Experimental data: 96h LC50 > 5 mg/L   Estimated data: ECOSAR LC50 (96 h) = 0.01 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 data: 48h EC50 > 4.8 mg/L 48h EC50 > 0.010 mg/L   21 d NOEC > 0.0057 mg/L 21 d NOEC = 0.34 mg/L   Estimated data: ECOSAR LC50 (48 h) = 0.004 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		Experimental data: 72h-EC50 > 4.5 mg/L (growth rate) 72h-NOEC = 0.51 mg/L (growth rate)   Estimated data: ECOSAR EC50 (96 h) = 0.856 mg/L (Chemical may not be soluble enough to measure this predicted effect).	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 data: Key study: LD50>5000 mg/kg bw (rats)	Experimental results: LD50 = 461 mg/kg
Acute Inhalation		No data	No data
Acute Dermal		No data	Experimental results: LD50 > 4000 mg/kg
Skin irritation / Eye irritation		No data	Experimental results: Not a skin irritant. Eye irritant.
Skin sensitisation		No data	Experimental results: Skin sensitiser
Repeated Dose		Experimental results: NOAEL from chronic study: 12.7 mg/kg bw/day (male rats) 15.1 mg/kg bw/day (female rats)	No data
Genetic Toxicity in vitro	Gene mutation in bacteria	Experimental results: Negative	No data
	Chromosomal aberration	Experimental results: Negative	No data
	Mammalian gene mutation	No data	No data
Genetic Toxicity in vivo		No data	No data
Carcinogenicity		No data	No data
Reproductive Toxicity: developmental toxicity		Experimental results: Developmental toxicity: NOAEL maternal toxicity = 93.5 mg/kg bw/day NOAEL developmental toxicity = 375 mg/kg bw/day (highest dose tested).	Developmental toxicity: Read-across: NOAEL maternal toxicity = 72 mg/kg bw/day NOAEL developmental toxicity = 290 mg/kg bw/day (highest dose tested).

Applicant's summary and conclusion

Conclusions:

The NOAEL for maternal toxicity is 72 mg/kg bw/day and the NOAEL for developmental toxicity was 290 mg/kg bw/day (the highest dose tested).

Executive summary:

The analogue CAS No. 119-47-1 (6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol) which shares the same functional group (alkylphenol) with the substance CAS no. 88-27-7 (2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 119-47-1 can be used for the read-across approach.

The NOAEL for maternal toxicity is 72 mg/kg bw/day and the NOAEL for developmental toxicity was 290 mg/kg bw/day (the highest dose tested).