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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
The aim of this study is to assess the hazardous potential of the substance 10-(2, 5-Dihydroxyphenyl)-10H-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO-HQ) with respect to repeated dose toxicity and related reproductive and developmental toxicity effects. The assessment will include expert analysis on the reactivity and possible transformations of the target chemical as well as in silico predictions.

Data source

Reference
Reference Type:
other: QSAR
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
no guideline followed
Guideline:
other: QSAR prediction
Principles of method if other than guideline:
Experimental developmental toxicity data for HQ and a phosphinate (CAS 84434-11-7, ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate), that could be used as analogue to DOPO are available in TB (see Table 4 presented below-"Experimental Developmental toxicity (NOEL/NOAL) data for HQ fragment and another phosphinate which could be considered as analogous to DOPO").

According to the ECHA dossiers [17, 23] the experimental studies for both chemicals are conducted according to OECD TG 414 (Prenatal Developmental Toxicity Study). The study of HQ gave no indication for a potential developmental or reproductive hazard of hydroquinone [23]. Krasavage et. al (1992) also reports that the HQ is not selectively toxic to developing conceptuses and does not appear to be a developmental toxicant [24].



GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
9-(2,5-dihydroxyphenyl)-8-oxa-9λ⁵-phosphatricyclo[8.4.0.0²,⁷]tetradeca-1(14),2,4,6,10,12-hexaen-9-one
EC Number:
619-409-6
Cas Number:
99208-50-1
Molecular formula:
C18H13O4P
IUPAC Name:
9-(2,5-dihydroxyphenyl)-8-oxa-9λ⁵-phosphatricyclo[8.4.0.0²,⁷]tetradeca-1(14),2,4,6,10,12-hexaen-9-one
Test material form:
solid: particulate/powder

Test animals

Species:
other: QSAR predictions on several anaogues

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Details on results:
Experimental developmental toxicity data for HQ and a phosphinate (CAS 84434-11-7, ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate), that could be used as analogue to DOPO are available in TB (see Table 4 as was shown).

According to the ECHA dossiers [17, 23] the experimental studies for both chemicals are conducted according to OECD TG 414 (Prenatal Developmental Toxicity Study). The study of HQ gave no indication for a potential developmental or reproductive hazard of hydroquinone [23]. Krasavage et. al (1992) also reports that the HQ is not selectively toxic to developing conceptuses and does not appear to be a developmental toxicant [24].

The maternal toxicity of the phosphinate (CAS 84434-11-7) was assessed to be 100 mg/kg bd/d [23]. In fetuses, three skeletal variations affecting the skull, ribs and sternebrae were assessed as treatment-related but not as adverse. These minor and reversible effects indicate a developmental delay which is reversible. Thus, the no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 300 mg/kg bw/d while the no observed effect level (NOEL) for prenatal developmental toxicity is 100 mg/kg bw/d.

Both structures (HQ and CAS 84434-11-7) with their experimental data are used to predict the target chemical. NO(A)EL of DOPO-HQ is predicted to be
174 mg/kg bw/d (Figure 9, see attached full report).

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Based on:
other:
Remarks:
QSAR prediction
Basis for effect level:
other: QSAR data
Remarks on result:
other:
Remarks:
QSAR data

Results (fetuses)

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
174 mg/kg bw/day
Based on:
other: QSAR data
Sex:
not specified
Basis for effect level:
other: QSAR data
Remarks on result:
other: QSAR data

Fetal abnormalities

Key result
Abnormalities:
effects observed, treatment-related
Localisation:
skeletal: skull
skeletal: rib
Description (incidence and severity):
In fetuses, three skeletal variations affecting the skull, ribs and sternebrae were assessed as treatment-related but not as adverse. These minor and reversible effects indicate a developmental delay which is reversible.

Overall developmental toxicity

Key result
Developmental effects observed:
not specified
Lowest effective dose / conc.:
100 mg/kg bw/day
Treatment related:
yes

Applicant's summary and conclusion

Conclusions:
Conclusions on developmental toxicity:
 The NO(A)EL of DOPO-HQ with respect to developmental toxicity is predicted to be 174 mg/kg bw/d.
 Based on the phosphinate properties with respect to AChE inhibition and the available experimental data for HQ and DOPO`s analogues (CAS 84434-11-7), it could be assumed that the target chemical (DOPO-HQ) will have no or very low developmental toxicity.
Executive summary:

Experimental developmental toxicity data for HQ and a phosphinate (CAS 84434-11-7,ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate), that could be used as analogue to DOPO are available in TB(seeTable 4below).

 

Table 4.Experimental Developmental toxicity (NOEL/NOAL) data for HQ fragment and another phosphinate which could be considered as analogous to DOPO

 

Exp. data

(test organism)

Toolbox database

HQ

NOEL = 25 mg/kg bdwt/d

(rabbit)

ECHA CHEM

NOEL = 75 mg/kg bdwt/d

(rabbit)

ECHA CHEM

NOEL = 100 mg/kg bdwt/d

(rat)

ECHA CHEM

NOEL = 100 mg/kg bdwt/d

(rat)

ECHA CHEM

CAS 84434-11-7

NOEL = 100 mg/kg bdwt/d

ECHA CHEM

NOAEL = 300 mg/kg bdwt/d

ECHA CHEM

 

According to the ECHA dossiers [17, 23] the experimental studies for both chemicals are conducted according to OECD TG 414 (Prenatal Developmental Toxicity Study). The study of HQ gave no indication for a potential developmental or reproductive hazard of hydroquinone [23].Krasavage et. al (1992) also reports that the HQ is not selectively toxic to developing conceptuses and does not appear to be a developmental toxicant [24].

The maternal toxicity of the phosphinate (CAS 84434-11-7) was assessed to be 100 mg/kg bd/d [23].In fetuses, three skeletal variations affecting the skull, ribs and sternebrae were assessed as treatment-related but not as adverse. These minor and reversible effects indicate a developmental delay which is reversible. Thus, the no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 300 mg/kg bw/d while the no observed effect level (NOEL) for prenatal developmental toxicity is 100 mg/kg bw/d.