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Toxicological information

Developmental toxicity / teratogenicity

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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)

open allclose all
Dose descriptor:
NOAEL
Effect level:
72 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
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).