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

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

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:

Based on metabolism models generated with OASIS TIMES, benzylamines metabolites are formed from the substance 2,6-Di-tert-butyl-alpha-(dimethylamino)-p-cresol (CAS 88-27-7). The substance CAS No. 1477-55-0 presents the functional group benzylamine. Therefore, the results obtained with the substance CAS No. 1477-55-0 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 from experimental data on an analogue.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

m-phenylenebis(methylamine)

EC Number:

216-032-5

EC Name:

m-phenylenebis(methylamine)

Cas Number:

1477-55-0

IUPAC Name:

1,3-phenylenedimethanamine

Details on test material:

- Molecular formula (if other than submission substance): C8H12N2
- Molecular weight (if other than submission substance): 136.2
- Smiles notation (if other than submission substance): c1c(cccc1CN)CN
- InChl (if other than submission substance): InChI=1S/C8H12N2/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5-6,9-10H2
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

870 mg/kg bw/day

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Based on metabolism models generated with OASIS TIMES, benzylamines metabolites are formed from the substance 2,6-Di-tert-butyl-alpha-(dimethylamino)-p-cresol (CAS 88-27-7).The substance CAS No. 1477-55-0 presents the functional group benzylamine. Therefore, the results obtained with the substance CAS No. 1477-55-0 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		1477-55-0	88-27-7
CHEMICAL NAME		Analogue 1,3-bis(aminomethyl)benzene	Target chemical 2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: No data	Experimental results: Handbook: 94 ºC
Boiling Point		Experimental results: 247 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: 0.0146 mm Hg 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)		Estimated data: 0.15	Estimated data: The calculated partition coefficient is 4.24 (EPI Suite, KOWWIN v1.68 estimate).
Water solubility		Estimated data: 6.64E+005 mg/L at 25 ºC	Experimental results: 10.7 mg/L at 20 ºC (pH 9.2)
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Estimated data: No readily biodegradable (BIOWIN v4.10)	Estimated data: No readily biodegradable (BIOWIN v4.10)
Anaerobic Biodegradation		No data	No data
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Key study: Estimated data: 96-h LC50 for fish is 312.233 mg/l (ECOSAR v1.00a, aliphatic amines class). 96-h LC50 for fish is 464.593 mg/l (ECOSAR v1.00a, benzyl 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		Key study: Estimated data: 48-h LC50 for Daphnia is 21.47 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		Key study: Estimated data: 96-h EC50 for green algae is 5.044 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		No data	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		Repeated dose toxicity: oral: Key study: 28-day study in rats: NOEL 150 mg/kg/day	Read-across: NOEL 290 mg/kg bw/day
Genetic Toxicity in vitro	Gene mutation in bacteria	Key study: Negative	Read-across: Negative
	Chromosomal aberration	Key study:  Negative	Read-across: Negative
	Mammalian gene mutation	Key study:  Negative	Read-across: Negative
Genetic Toxicity in vivo		No data	No data
Carcinogenicity		No data	No data
Reproductive Toxicity: developmental toxicity		Key study: Experimental results: Screening for reproduction toxicity: Test chemical administration had no influence on mating ability, fertility, duration of oestrus or duration of pregnancy and parturition.   NOAEL for reproductive/developmental toxicity (F1 offspring) = 450 mg/kg bw/day.	Read-across: NOAEL for reproductive/developmental toxicity (F1 offspring) = 870 mg/kg bw/day.

Applicant's summary and conclusion

Conclusions:

No adverse effects were observed in terms of copulation, fertility, delivery and nursing of parents, and the viability, body weight and morphology of offsprings.

Based on experimental data, the read-across approach is applied and the NOAEL for reproductive/developmental toxicity (F1 offspring) was 870 mg/kg b.w./day.

Executive summary:

Based on metabolism models generated with OASIS TIMES, benzylamines metabolites are formed from the substance 2,6-Di-tert-butyl-alpha-(dimethylamino)-p-cresol (CAS 88-27-7).The substance CAS No. 1477-55-0 presents the functional group benzylamine. Therefore, the results obtained with the substance CAS No. 1477-55-0 can be used for the read-across approach.

No adverse effects were observed in terms of copulation, fertility, delivery and nursing of parents, and the viability, body weight and

morphology of offsprings.

NOAEL for reproductive/developmental toxicity (F1 offspring) was 870 mg/kg b.w./day.